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••• Sayin HÜ, Schenck CH Desire-Pleasure-Orgasm ••• A Multidisciplinary Academic Journal Published Quarterly by CİSEATED-ASEHERT • Original Review SexuS Journal 4 (11): 907-946 MARCH Part-2 Neuroanatomy and Neurochemistry of Sexual Desire, Pleasure, Love and Orgasm Introduction

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Pleasure is a mental and emotional state that humans and other animals experience as positive, enjoyable, satisfying, giving joy and happiness or worth seeking. It may include other mind states such as happiness, entertainment, enjoyment, ecstasy, and euphoria, with peak experiences. According to the "incentive salience model" pleasure has three components: "wanting and motivation", "learning" and "liking-pleasure". Different brain regions cooperatively work together for each of these constituents. Since most of the data to establish this model came from animal studies, for human beings a more profound and complex model needs to be established. During the onset of pleasure or sensuality, dopaminergic neurons in ventral tegmental area (VTA) fire and their projections to the nucleus accumbens (NA) release dopamine which participates in the complex psychological processes of learning and liking. Similar episodes occur during the onset of sexual pleasure and human orgasm. Some complex human phenomena, such as passionate love or expanded orgasms, can be regarded as peak experiences, which the animal kingdom does not seem to experience. During passionate love, for instance, the release of some neurotransmitters, such as dopamine, oxytocin, and norepinephrine, is enhanced, while serotonin levels drop; in some fMRI studies, it is shown that some brain regions and "hedonic hot spots" are activated. During the female orgasm, VTA, NA, anterior cingulate, insula, amygdala, hippocampus, and hypothalamus are activated. In this article neuroanatomical, neurophysiological, neurochemical components of pleasure, love, motivation and orgasm, which lead to impressive behavioral changes, are discussed. Also, the phenomenon of experiencing sexual pleasure during the sleep found with the parasomnia "Sexsomnia" and also "Epileptic Sexsomnia", both for the affected person and the bed partner will be discussed, with further research encouraged on this intriguing new clinical and clinical research area.
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SexuS Journal www.sexusjournal.com Winter-2019 │Volume: 04 │Issue: 11 │Pages: 907-946
◦◦◦ Sayin HÜ, Schenck CH Desire-Pleasure-Orgasm ◦◦◦ ISSN 2536-5185 (web) ISSN 2536-5169 (print)
A Multidisciplinary Academic Journal Published Quarterly by CİSEATED-ASEHERT www.ciseated.org www.sexusjournal.com 907
Winter 2019, V:4; Issue: 11, March 31st, 2019
Psychopharmacology ● Neuroanatomy
Neuroscience ● Pleasure ● Love ● Orgasm
Original Review
ISSN 2536-5185 (web
ISSN 2536-5169 (print)
SAYIN HÜ
SCHENCK CH
Neuroanatomy-Neurochemistry:
Desire, Pleasure, Love & Orgasm
SexuS Journal 4 (11): 907-946 MARCH Part-2
Neuroanatomy and Neurochemistry of
Sexual Desire, Pleasure, Love and Orgasm
H. Ümit Sayin and Carlos H. Schenck
Abstract:
Pleasure is a mental and emotional state that humans and other animals experience as positive, enjoyable, satisfying, giving joy
and happiness or worth seeking. It may include other mind states such as happiness, entertainment, enjoyment, ecstasy, and
euphoria, with peak experiences. According to the “incentive salience model” pleasure has three components: “wanting and
motivation”, “learning” and “liking-pleasure”. Different brain regions cooperatively work together for each of these
constituents. Since most of the data to establish this model came from animal studies, for human beings a more profound and
complex model needs to be established. During the onset of pleasure or sensuality, dopaminergic neurons in ventral tegmental
area (VTA) fire and their projections to the nucleus accumbens (NA) release dopamine which participates in the complex
psychological processes of learning and liking. Similar episodes occur during the onset of sexual pleasure and human orgasm.
Some complex human phenomena, such as passionate love or expanded orgasms, can be regarded as peak experiences, which
the animal kingdom does not seem to experience. During passionate love, for instance, the release of some neurotransmitters,
such as dopamine, oxytocin, and norepinephrine, is enhanced, while serotonin levels drop; in some fMRI studies, it is shown
that some brain regions and “hedonic hot spots” are activated. During the female orgasm, VTA, NA, anterior cingulate, insula,
amygdala, hippocampus, and hypothalamus are activated. In this article neuroanatomical, neurophysiological, neurochemical
components of pleasure, love, motivation and orgasm, which lead to impressive behavioral changes, are discussed. Also, the
phenomenon of experiencing sexual pleasure during the sleep found with the parasomnia “Sexsomnia” and also “Epileptic
Sexsomnia”, both for the affected person and the bed partner will be discussed, with further research encouraged on this
intriguing new clinical and clinical research area.
KEY WORDS: pleasure, hedonic hot spot, reward, orgasm, sexual pleasure, pleasure center, cingulate, insula, amygdala, hippocampus,
hypothalamus, n. accumbens, ventral tegmental area, addiction, dopamine, oxytocin, liking, motivation, sexsomnia, epileptic sexsomnia
SexuS Journal ● Winter 2019 ● 4 (11): 907-946
Corresponding Author: Ümit Sayin, M.D., PhD
Address: Institute of Forensic Sciences, İstanbul University,
Cerrahpasa, Aksaray, İstanbul
ASEHERT-CİSEATED (www.ciseated.org) www.humitsayin.com
humitsayin@gmail.com
Prof. Carlos H. Schenck, MD: schen010@umn.edu
University of Minnesota, Department of Psychiatry, 2450
Riverside Ave, Minneapolis, MN, 55454, USA.
Received December 10th 2018; Accepted January 20th 2019;
Published March, 2019.
© Copyright 2019, Ü.Sayin
SexuS Journal www.sexusjournal.com Winter-2019 │Volume: 04 │Issue: 11 │Pages: 907-946
◦◦◦ Sayin HÜ, Schenck CH Desire-Pleasure-Orgasm ◦◦◦ ISSN 2536-5185 (web) ISSN 2536-5169 (print)
A Multidisciplinary Academic Journal Published Quarterly by CİSEATED-ASEHERT www.ciseated.org www.sexusjournal.com 908
Pleasure was described as a
positive feedback mechanism that
motivates the organism to seek the
situation it has just found pleasurable, and
to avoid past circumstances that caused
pain, anxiety, depression and sadness
(Freud, 1950).
Pleasure is a mental and emotional
state that humans and other animals
experience as positive, enjoyable,
satisfying, giving joy and happiness or
worth seeking. It may include other mind
states such as happiness, entertainment,
enjoyment, ecstasy, and euphoria, with
peak experiences, eventually. Some of the
former schools of psychology and
psychiatry described the concept of
pleasure as the “pleasure principle”, which
was regarded as innate and instinctive.
Pleasure was described as a positive
feedback mechanism that motivates the
organism to seek the situation it has just
found pleasurable, and to avoid past
circumstances that caused pain, anxiety,
depression and sadness (Freud, 1950,
Sayin 2019).
The experience of pleasure is very
subjective and different individuals
experience different kinds and amounts of
pleasure when they face the same
situation. Many pleasurable experiences
are associated with satisfying basic
biological drives, such as eating, sleeping,
sexual pleasure and orgasm, motility-
exercise, and seeking a state of feeling
good and being content (and not
unhappy), (Schultz, 2015).
Based upon the incentive salience
model of reward, an intrinsic reward has
two components: a "wanting" or desire
component that is reflected in approach
behavior, and a "liking" or pleasure
component that is reflected in consuming
behavior (Schultz, 2015; Berridge, 2008,
2009).
Pleasure is a component of reward, but
some rewards are not that pleasurable
(Schultz, 2015; Berridge, 2007, 2008, 2009).
Stimuli that are naturally pleasurable, and
therefore attractive, are known as intrinsic
rewards (for instance the imagining of a
nude and beautiful woman for a man, an
instinctive and innate stimulus), whereas
stimuli that are attractive and motivate
approach behavior, but which hasn’t
passed through the genetic codes (and not
inherited) is not innate, are coined as
extrinsic rewards. Extrinsic rewards (e.g.,
money, fetish objects, and sexy objects, the
opposite sex for heterosexuals) are
rewarding as a result of a learned
association with an intrinsic reward. In
other words, extrinsic rewards function as
motivational magnets that elicit "wanting",
but not "liking (eventually pleasure)
reactions once they have been acquired
(Schultz, 2015; Berridge, 1998, 2007, 2009,
2015).
The reward system contains specific
brain pleasure centers or “hedonic hotspots
that mediate pleasure or "liking mood”
from intrinsic rewards. For instance, sex is
an instinct and it’s intrinsic; making love
to a woman is a learned behavior, while it
has some innate motives, as well, and it
involves “liking” and pleasure. Making
love to a woman results in ejaculation and
the whole making love session is full of
pleasure; where VTA dopaminergic
neurons start to fire and abundant
dopamine is released in the nucleus
accumbens (NA), which is perceived by
the pre-frontal cortex as pleasure-“liking
sensation or mood”. The reward is
pleasurable and happy consciousness”,
however this is a learned behavior; the id
SexuS Journal www.sexusjournal.com Winter-2019 │Volume: 04 │Issue: 11 │Pages: 907-946
◦◦◦ Sayin HÜ, Schenck CH Desire-Pleasure-Orgasm ◦◦◦ ISSN 2536-5185 (web) ISSN 2536-5169 (print)
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(instincts) has made an intrinsic reward
(pleasure), from an extrinsic reward
(woman, or making love to her); sex is a
learned behavior, because the outcomes of
sexual intercourse did not exist among the
intrinsic knowledge, but it is acquired
after some experiences. Since it is joyful, it
is “wanted”, “liked”, “gives pleasure” and
it is sought.
Pleasure Centers or
Hedonic Hot-Spots
Hedonic hotspots that have been
identified to date are: lateral thalamus (?),
nucleus accumbens (NA), ventral pallidum,
parabrachial nucleus, orbitofrontal cortex
(OFC), cingulate cortex and insular cortex
(Berridge, 2008, 2009, 2015, 2017; Schultz,
2015; Koob, 2009, 2010). Ventral Tegmental
Area (VTA) can also be counted as a hot
spot because it contains many
dopaminergic neurons that project into
NA. The posterior ventral pallidum contains
a hedonic hotspot, while the anterior
ventral pallidum contains a hedonic cold
spotwhich induces a negative emotion,
such as fear and disgust, when stimulated.
Microinjections of opioids,
endocannabinoids, amphetamines and
orexin are capable of enhancing the liking
effect in these hotspots (Berridge, 2008,
2009, 2015, 2017; Koob, 2010; Volkow,
2007; Sayin, 2019). In some structures of
the brain there are hedonic hot spots and
cold spots very close to each other and
interconnected, receiving projections from
VTA, acute dopamine releasing events or
drugs, may activate both of them, then
there may be reward (pleasure), but also
some negative emotion (such as anxiety).
When “hot spots” and “cold spots” are
activated together, the balance between
them becomes important; that is why
some drugs or pleasure-inducing joyful
events have different influences in
different people, because of the variety of
neuronal wiring and circuitry, as well as
the amount of neurotransmitters released
(primarily dopamine and oxytocin). For
instance some people are, inherently, more
susceptible to generalized anxiety
disorder, which may be the outcome of
their limbic circuitry; or some people can
become easily addicted, while some
people are resistant to addiction, such as
alcoholism or substance abuse.
Sexual motivation, desire, pleasure
and orgasm, also originate from the same
limbic reward-pleasure circuitry. Sexual
pleasure is the nature’s trap, to compel
human beings to reproduce and it is one of
most powerful driving forces of life;
sometimes so powerful that loss of the
loved one may drive a person to severe
depression and even to suicide. Love,
sexual pleasure and orgasm in H. sapiens
are far more complicated phenomena,
compared to the mating of animals,
which require higher cortical centers to
activate with many subcortical structures.
However, the same neurochemicals
participate in the induction of sexual
pleasure, such as dopamine and oxytocin.
Komisaruk et al. reported, from some
fMRI studies, that during the orgasms
induced by vaginal-cervical stimulation or
clitoral stimulation, hypothalamic
paraventricular nucleus (where oxytocin is
initially released), amygdala, hippocampus,
nucleus accumbens (NA), nucleus Caudatus
(NC), insula, preoptic area, some basal
ganglions, cerebellum, anterior cingulate
gyrus, insular-parietal and prefrontal cortices
were activated (Komisaruk, 2005, 2006,
2011; Wise, 2017; Jannini, 2018). As it is
seen during orgasm reward”, same or
similar regions in the brain (compared to
that of animals) are activated (written in
red). In human beings there may be more
hedonic hot spots” or “cold spots” compared
to experimental animals. By means of
sophisticated technology and imaging
techniques, now we are able to see how
human data fits with the findings
emerging from animal experiments, since
SexuS Journal www.sexusjournal.com Winter-2019 │Volume: 04 │Issue: 11 │Pages: 907-946
◦◦◦ Sayin HÜ, Schenck CH Desire-Pleasure-Orgasm ◦◦◦ ISSN 2536-5185 (web) ISSN 2536-5169 (print)
A Multidisciplinary Academic Journal Published Quarterly by CİSEATED-ASEHERT www.ciseated.org www.sexusjournal.com 910
our limbic system has formed as a result of
at least 500 million years of evolution since
the Cambrian Explosion, having similar
neurophysiological structures that our
grand ancestors had also conveyed
(Futuyma, 1997; Bownds, 1999).
In some cerebral blood flow PET
studies Georgiadis et al. have found that
during arousal and orgasm, some parts of
the brain shut down and are deactivated,
while some parts are activated. During
orgasm orbitofrontal cortex of prefrontal
cortex is deactivated; during arousal left
inferior parietal lobule and post central gyrus
are activated; however right amygdala and
left fusiform gyrus, right mid temporal gyrus,
inferior temporal gyri are deactivated.
During orgasm, left cerebellar vermis
(frontal lobe) is activated in both men and
women. In women, during orgasm, right
insula, is activated more profoundly than
in men. In regional cerebral blood low
studies (rCBF), Georgiadis et al. have
found that during clitoral stimulation,
blood flow is increased at the right
somatosensorial cortex; during clitoral
orgasm, rCBF is decreased at the left
orbitofrontal cortex, inferior temporal gyrus
and anterior temporal lobe; the increase of
rCBF, is detected at the caudate nucleus
(CN) and cerebellar nuclei (Georgiadis,
2006, 2009).
Female orgasm is a reward for sexual
instincts, motivation and acts; sexual
pleasure and orgasm have many similar
mechanisms to that of reward seeking
behavior, using the same reward and
pleasure centers, hedonic hot spots and
similar neurochemicals. During a
passionate love experience, also NA and
VTA are activated (Diamond, 2012; Aron,
2005; Ortigue, 2007).
The results coming from animal
studies (mostly rats), have been tested in
live human subjects by using very
sophisticated imaging techniques, such as
fMRI. It was shown that, when there is
pleasure the following areas of the brain
may become activated ( Komisaruk, 2005,
2006, 2011; Wise, 2017; Jannini, 2018;
Berridge, 2007a, b, 2008a, b, 2009, 2015;
Richard, 2013, Castro, 2017; Kringelbach,
2012; Ortigue, 2007, 2010; Aron, 2005;
Maravilla, 2007, 2008; Meston, 2000):
thalamus and/or lateral hypothalamus
(questionable ??)
nucleus accumbens (NA)
ventral tegmental area (VTA)
ventral pallidum
insula
cingulate cortex
prefrontal cortex
orbitofrontal cortex
septum
Homo sapiens is a pleasure seeking
higher primate (Bownds, 1999; Futuyma,
1997). He /she escapes from dysphoria,
stress, anxiety and depression and choses
the behaviors that lead him/her to
euphoria, anxiolysis, relieving his / her
depression. For instance, drug usage,
alcohol addiction, over eating etc. are the
clinical signs of the attempts to relieve
stress, anxiety and depression and attain
mild sedation, elevated mood,
contentment, and even euphoria.
When it comes to sexual pleasure,
particularly for women, orgasmic
experience gives anti-depressant,
anxiolytic, sedative and analgesic effects
(Sayin, 2012, 2014, 2017-a,b,c, 2018-a,c),
mostly because of the rush of the
following neurochemicals (Sayin, 2012,
2014, 2015, 2017-b,c , 2018-a, 2019;
Kuchinska, 2009; Carter, 1992; Lee, 2009;
Magon, 2011; Kim, 2015; Meston, 2000):
Dopamine
Oxytocin
Prolactin
Epinephrine & norepinephrine
Endorphins
Components of Motivation
and Pleasure
During the last several decades,
neuroscientists have attained very
SexuS Journal www.sexusjournal.com Winter-2019 │Volume: 04 │Issue: 11 │Pages: 907-946
◦◦◦ Sayin HÜ, Schenck CH Desire-Pleasure-Orgasm ◦◦◦ ISSN 2536-5185 (web) ISSN 2536-5169 (print)
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important clues about the neuroanatomy
and neurochemistry of pleasure and
happiness, which have three components
(Berridge, 2009):
Wanting and motivation
Learning and associations &
predictions
Liking and pleasure
Most of the researchers have focused
on these three steps of the components of
happiness. When we consider Homo
sapiens, there should be other steps
modified for humans to ascend according
to our studies and conceptualization of
other studies, because most incentive
salience model data” come from animal
studies (mostly, rats). Kent Berridge and
his colleagues have done some brilliant
laboratory work on defining pleasure and
the components of pleasure (Berridge,
1991, 1998, 2003, 2007, 2008, 2009, 2015).
The model of the neural substrates of
pleasure, liking and addiction depends on
animal experiments whereas the rats were
given “food” or “drugs” such as cocaine or
amphetamines, as a reward, and
microinjections of opioids, amphetamines,
orexin, endogenous cannabinoids (such as
anandamide) were placed into the hedonic
hot spots before or during the
experiments. The results derived from the
psychology of animals are too far removed
compared to H. sapiens to understand the
real nature of human psychology;
however, such research can give some
important hints, insights and clues to us
about what to investigate in human
beings.
When we discuss the components
of pleasure and human sexuality, some
findings derived from rat research using
food, cocaine and amphetamines (DA
increasing agents) as incentive salience
will not be able to explain many aspects of
the components of human behavior as a
model.
Our data on sexuality and results
coming from psychologists/psychology
schools and neuroscientists would be
suggesting ways and methods to
reorganize the components of pleasure as
above in Table-1 (Sayin, 2012, 2014, 2015-
a,b, 2017-a, b, c, 2018-a,c, 2019; Maslow,
1968; Taylor, 2000, 2002 ): (Table-1 and
Figs-1, 2, 3).
For a model designed for human beings,
we have to include, extreme pleasures and
some peak experiences of men and women
(e.g. ego-satisfaction, eating delicious
food, smelling a good fragrance, female
orgasm, love, ecstasy, listening to the
preferred music, other higher cortical
functions etc.), because rats cannot fall in
love, write poetry, experience meditation and
satori, make abstract deductions, eat specific
delicious food, communicate with language,
satisfy their ego (See: Cartoon-1); besides
female rats do not experience orgasms or
expanded orgasms, as found with the
human female. Orgasmic behavior is
mostly specific to the females of higher
primates and Homo sapiens (Sayin, 2012-a,
2014, 2015-a, 2017-a, 2018-a, 2019). Peak
experiences, a step further from extreme
pleasure and ecstasy, were also defined in
the pyramid of basic humanitarian needs
(Maslow, 1968), such as love, abstract
pleasures, expanded ESR orgasms,
nirvana-like experiences (Austin, 1999).
(See Figs 2,3 & 4; Tables 1-2-3)
SexuS Journal www.sexusjournal.com Winter-2019 │Volume: 04 │Issue: 11 │Pages: 907-946
◦◦◦ Sayin HÜ, Schenck CH Desire-Pleasure-Orgasm ◦◦◦ ISSN 2536-5185 (web) ISSN 2536-5169 (print)
A Multidisciplinary Academic Journal Published Quarterly by CİSEATED-ASEHERT www.ciseated.org www.sexusjournal.com 912
Figure-1: Hedonic hot spots or pleasure centers of the brain.
TABLE-1: Components of Happiness and Neuro-psychological Modulators of Pleasure
Wanting and
motivation
Learning and
associations
& predictions
Liking and
pleasure
Extreme pleasure
and ecstasy
(e.g. orgasm)
Peak experiences
(e.g. Love,
ESR orgasms)
Total Happiness
STEP-1
STEP-2
STEP-3
STEP-4
STEP-5
STEP-6
What Happens During Love: As a
Peak Experience?
Extensive neuroscience and
neuropharmacology research has been
accomplished about “falling in love in
human subjects (Bartels, 2000, 2004;
Emaluele, 2006; Esch, 2005; Zeki, 2007,
2010; Marazziti, 1999, 2003, 2004, 2010;
Fichetti, 2011; Fisher, 2004, 2010; Kim,
2017; Meston, 2000; Tarlaci, 2017), also
using fMRI techniques (Diamond, 2012;
Ortigue, 2010 ; Avevedao, 2012; Fonteille,
2010; Maravilla, 2002, 2007; Moulier, 2006;
Walter, 2008). Here, we will summarize
how brain chemistry is changed during
love.
As a summary of neurotransmitters
that are altered during passionate love for
men and women (See Fig-3):
Serotonin decreases very much
compared to normal (i.e. that of before
falling in love).
Dopamine increases very much
compared to normal.
Oxytocin increases very much
SexuS Journal www.sexusjournal.com Winter-2019 │Volume: 04 │Issue: 11 │Pages: 907-946
◦◦◦ Sayin HÜ, Schenck CH Desire-Pleasure-Orgasm ◦◦◦ ISSN 2536-5185 (web) ISSN 2536-5169 (print)
A Multidisciplinary Academic Journal Published Quarterly by CİSEATED-ASEHERT www.ciseated.org www.sexusjournal.com 913
compared to normal.
Stress hormone cortisol increases
slightly.
Norepinephrine is increased slightly;
adrenergic sympathetic autonomous
system is activated.
Vasopressin is increased.
Testosterone increases both in men
and women; hence libido and sexual
pleasure is increased.
In the case of love, being with or
making love with the loved one becomes a
super-reward and it is strived for
compulsively before long. Without any
sexual activity, even being together with
the lover is always sought; that person
becomes the most important individual in
her/his life.
What Kind of Behavioral Changes
Occur in Lovers In Response to
Neurotransmitter Changes?
Love, in human beings, is a
complex behavioral, emotional and
consciousness state and a peak experience”;
it requires many higher cortical functions
in coordination with many alterations in
the limbic circuitry. Brain chemistry
changes, for at least 6 months; in some
cases these changes may continue up to
two years or more. Generally the changes
determined in the blood and cerebrospinal
fluid (CSF) returns to normal in six
months (Esch, 2006; Marazziti, 1999-2003-
2004-2010 ; Tarlaci, 2017; Zeki, 2007-2010;
Fischetti, 2011; Sayin, 2017a-c, 2018a,
2019). The components emerging from the
genetic factors, subconscious, collective
unconsciousness, limbic system, learned
information and conditioning since
childhood, sexual preferences, fantasies,
childhood traumas, abstract thinking,
social norms and conditioning, social and
religious dogmas, biases, etc., contribute to
the development of love (Sayin, 2017-a,
2018-a).
Love can be accepted as a type of
obsessive compulsive behavior, while it
has some positive rewards and induces
happiness. Changes in the brain chemistry
are reflected to the psychology, behavior,
mood, motivation, desires, libido, pleasure
and contentment of the individual lover’s
emotions; rewarding and inducing
happiness. During love, sexual pleasure
and orgasms are enhanced, particularly in
women. The better and more intense the
orgasms are, the more oxytocin is released;
hence, love strengthens and more
attachment occurs.
Oxytocin, which is secreted from
hypothalamic paraventricular nucleus and
posterior pituitary, is a hormone in the
bloodstream and a neurotransmitter in the
brain. Acute oxytocin release induces
many behavioral changes; it is the specific
neurotransmitter of love, sexual pleasure,
orgasm, bonding, empathy, attachment,
and motherhood (see below for oxytocin)
(Sayin, 2012, 2014, 2015, 2017-b,c , 2018-a,
2019; Kuchinska, 2009; Carter, 1992; Lee,
2009; Magon, 2011; Kim, 2015) .
Neuro-Imaging Studies of Passionate
Love, Sexual Desire and Arousal
The parieto-temporo-occipital region
induces the perception of integrity of the
self with the environment. Activation of
this region makes the person differentiate
self from the outer world and space.
During love this region is inactivated (Zeki,
2007; Bartels & Zeki, 2000; Esch & Stefano,
2005); hence the individuals may perceive
a diminishing ego, or an ego-loss, which is
replaced by a perception of integration
and unification (with the partner, with the
nature or universe) feeling (Zeki, 2007;
Bartels & Zeki, 2000; Esch & Stefano,
2005). Similar feelings and mood may be
experienced in some mystical
phenomenon (Sayin, 2016, 2017-d) and
during the influence of psychoactive
substances (Sayin, 2015-b, 2016, 2017-d,e,
2018-b, 2019).
SexuS Journal www.sexusjournal.com Winter-2019 │Volume: 04 │Issue: 11 │Pages: 907-946
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Cartoon-1: An ironical representation and depiction of anthropomorphized animals having peak experiences.
Frogs have always been associated with meditation and nirvana by humans; rats have been depicted as
reward mostly cheese- seeking and stealing animals in the cartoons or animations, although this is a human
abstraction and humor. The topmost peak experience of a rat is probably attaining limitless food and mating
with as many female rats as possible, or pressing the lever to deliver electric shocks into pleasure centers in a
BSR experiment; the same is valid for a frog. The neo-cortex of H. sapiens requires much more to name it as a
peak experience”. (cartoon is drawn and created by Dr. Ümit Sayin, for this article)
Figure-2: Incentive salience model for wanting, learning and liking. References: Freud, 1950, Berridge, 1991, 1998, 2003, 2007,
2008, 2009, 2015; Komisaruk, 2005, 2006, 2011; Wise, 2017; Jannini, 2018; Sayin, 2012, 2014, 2015-a,b, 2017-a, b, c, 2018-a,c; Maslow,
1968; Taylor, 2000, 2002; Schultz, 2015. Upward arrow depicts the amount of dopamine released and increased dopamine discharge.
SexuS Journal www.sexusjournal.com Winter-2019 │Volume: 04 │Issue: 11 │Pages: 907-946
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Figure-3: Neurotransmitter and behavioral changes in the brain during passionate love.
References: Bartels, 2000, 2004; Emaluele, 2006; Esch, 2005; Zeki, 2007, 2010; Marazziti, 1999, 2003, 2004, 2010;
Fichetti, 2011; Fisher, 2004, 2010; Kim, 2017; Meston, 2000; Tarlaci, 2017; Freud, 1950; Diamond, 2012; Ortigue, 2010.
In an fMRI study of 7 men and 10
women, who were deeply in love; in men,
dorsal insula region, which seems to
correlate with penile erection and some
other regions which were correlated with
seeing and distinguishing faces were
activated much more compared to
women; whereas in women the brain
regions which are correlated with
romanticism are activated more
profoundly compared to men (Ortigue,
2010; Tarlaci, 2017).
Aron et al. (2005) also focused on
the early stage passionate love, and found
that when participants looked at the face
of their partner and thought about
pleasurable, non-sexual events involving
the partner, activation was detected in the
right caudate nucleus and the ventral
tegmental area (VTA), whereas the amygdala
showed deactivation. Caudate nucleus and
VTA are the most consistent regions
associated with romantic love (Acevedo et
al. 2011, Aron et al. 2005, Bartels & Zeki
2000, Ortigue et al. 2007, Xu et al. 2010),
consistent with the fact that these
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dopamine-rich regions are strongly
associated with reward and goal-directed
behavior, supporting the notion that
romantic love is an intense motivational
state and extraordinary experience which
also uses the reward-pleasure circuitry
and some of the “hedonic hot spots”.
The research using priming tasks
(Bianchi-Demicheli et al. 2006, Ortigue et
al. 2007) has demonstrated that the
dopaminergic system-mediated
motivational state of romantic love has
powerful effects on cognition, facilitating
performance on verbal decision tasks.
This work may be regarded for
demonstrating the possibility that
although activated areas of the loving
brain may be localized in some “hedonic
hot spots”, the influence of love on other
brain functions can be spacious and
prevalent, because of the variety of
enhanced neural associative network
(Bianc Demicheli et al. 2006; Tarlaci, 2017).
Apart from love, during usual
sexual encounters, certain brain regions do
appear to be activated in response to
sexual stimuli, such as the hypothalamus,
putamen, visual cortical areas and
inferotemporal cortex, the orbitofrontal cortex,
anterior cingulate cortex (ACC), parietal
cortex, temporo-parietal junction, insula,
ventral striatum, anterior temporal areas,
interior frontal and cingulate areas, amygdala,
and basal ganglia (Fonteille 2010; Karama et
al. 2002; Maravilla 2007, 2008; Moulier et al.
2006; Walter et al. 2008; Komisaruk, 2005,
2006, 2011; Jannini, 2018; Wise, 2017). As
we can see hedonic hot spots(in red) for
the reward-pleasure circuitry in the limbic
system are also included to the list.
The putamen and caudate nucleus are
both associated with reward and
motivational states, desire, sexual arousal.
Their joint relevance for both sexual desire
and romantic love reflects the fact that
love, sexual desire and arousal all involve
strong motivation to pursue the love
object” or the sexual pleasure object(Sayin,
2017-a, b, 2018-a). The relevance of the
anterior cingulate cortex (ACC-center of self-
knowledge, subjective feelings and
perception of the self) for both love and
sexual desire is significant, when we
remember that the specific region of the
ACC was found to be activated in Bartel’s
(2000) study of love-specific brain
activation (Diamond, 2012; Tarlaci, 2017).
Conclusion: Very similar
neuroanatomical regions in the brain are
initially activated during incentive
salience, seeking pleasure-reward,
learning-retrieving pleasure mood”, sexual
pleasure, orgasm and love. Also similar
neurotransmitter mechanisms are
involved in all of them, while the quantity
and variety of the neurotransmitters may
change in different specific regions of the
brain in intense pleasure (e.g. orgasm) or
peak experiences (e.g. love and expanded
orgasms) (Figs-3 & 4). In love, with intense
orgasms, or extended orgasms, it is
obvious that many other higher cortical
centers are also involved as well as more
neurotransmitter systems may take part in
the process. Thus, we can conclude that
there are further steps to be taken for the
status after incentive behavior and
pleasure for human beings to be classified.
Neuroimaging Studies during Sexual
Stimulation and Orgasm
Komisaruk et al. have done
extensive research on the activation of
brain regions, during stimulation of
nipple, clitoris, vagina & cervix, arousal
and orgasm by using fMRI technique
(Komisaruk et al., 2003, 2004, 2005, 2006,
2011; Wise, 2017; Jannini, 2018). By self-
stimulation of clitoris, vagina and cervix
the overlapping regions of sensory cortex
and cortex region overlapping with the
innervation of pudental, pelvic and
hypogastric nerves, were activated
(Komisaruk, 2006; Jannini, 2018). Nipple
self-stimulation activated paracentral
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lobule, interestingly which also overlaps
with the areas that are activated during
genital-self stimulation (Allen, 2016;
Komisaruk, 2011, 2013). In the brain,
stimulation of nipples is also perceived as
genital stimulation, as well as it induces
oxytocin release. Prior to orgasm, they
have found that amygdala, hippocampus,
nucleus accumbens, hypothalamus, septum,
anterior cingulate, insula and VTA were
activated with also dorsal raphe
(Komisaruk, 2011; Wise, 2017; Jannini,
2018). (See Figs 3, 5, 6,7)
Orgasm:
At orgasm, nucleus accumbens (NA)
and VTA areas were both activated. These
regions play great roles in dopaminergic
transmission, reward-pleasure reaction
and VTA projects into NA, where
dopamine release creates cascades of
reactions that may alter learning, memory,
synaptic plasticity and behavior.
Dopaminergic agonists can promote
sexual response, pleasure and orgasm;
while dopaminergic antagonists attenuate
sexual response and orgasm (Komisaruk,
2006).
The anterior cingulate and insula are
activated at orgasms, but they can also be
activated by painful stimuli (Pukall, 2005;
Casey, 1994, 2001). There is a possibility
that pain and orgasm may be using similar
or the same spinothalamic pathways, a
neurophysiological mechanism which can
explain why some women and men enjoy
mild pain and pleasure/orgasm together in
BDSM sessions. Also it is shown that
female orgasm is analgesic (Whipple, 1985;
Steinman, 1983; Komisaruk, 2006),
probably due to the release of oxytocin,
which has also analgesic effects, and
endogenous opioids. This can also explain
how mild pain and orgasmic pleasure can
be interchangeable with each other.
The putamen and caudate nucleus are
both associated with reward and
motivational states, desire, sexual arousal.
Their joint relevance for both sexual desire
and romantic love reflects the fact that
love, sexual desire and arousal all involve
strong motivation to pursue the love
object” or the sexual pleasure object(Sayin,
2017-a, b, 2018-a). The relevance of the
anterior cingulate cortex (ACC-center of self-
knowledge, subjective feelings and
perception of the self) for both love and
sexual desire is significant, when we
remember that the specific region of the
ACC was found to be activated in Bartel’s
(2000) study of love-specific brain
activation (Diamond, 2012; Tarlaci, 2017).
(See Figs 5, 6, 7)
Conclusion: Very similar
neuroanatomical regions in the brain are
initially activated during incentive
salience, seeking pleasure-reward,
learning-retrieving pleasure mood”, sexual
pleasure, orgasm and love. Also similar
neurotransmitter mechanisms are
involved in all of them, while the quantity
and variety of the neurotransmitters may
change in different specific regions of the
brain in intense pleasure (e.g. orgasm) or
peak experiences (e.g. love and expanded
orgasms) (Fig-4). In love, with intense
orgasms, or extended orgasms, it is
obvious that many other higher cortical
centers are also involved as well as more
neurotransmitter systems may take part in
the process. Thus, we can conclude that
there are further steps to be taken for the
status after incentive behavior and
pleasure for human beings to be classified.
(See Figs 1, 2, 3, 4; Tables 1, 2, 3, 4).
SexuS Journal www.sexusjournal.com Winter-2019 │Volume: 04 │Issue: 11 │Pages: 907-946
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Figure-4: Incentive salience model for wanting, learning and liking, reassessed with the alterations of
neurotransmitters. References: Berridge, 1991, 1998, 2003, 2007, 2008, 2009, 2015; Komisaruk et al., 2005,
2006, 2011; Wise, 2017; Jannini, 2018; Sayin, 2012, 2014, 2015-a,b, 2017-a, b, c, 2018-a,c; Maslow, 1968; Taylor,
2000, 2002; Schultz, 2015. Upward arrow depicts the amount of dopamine released and increased dopamine or
other neurotransmitters’ discharge.
Table-2: Alterations of Behavior in Response to Neurotransmitter Changes During Love
Decrease of Serotonin
Increase of Dopamine
Increased obsession and compulsion
Increased aggression
Mood instability, alterations of mood
Contributes better and intense orgasm in women,
particularly.
May induce premature ejaculation in men
Decreases sadness and unhappy feelings
Increases motivation
Increases joy, happiness, delight
Increases pleasure taken from the love itself
Increases pleasure during making love
Increases the intensity of orgasms particularly in
women; very powerful and multiple orgasms
Abolishes anxiety and depression
Increases attachment to the lover
Addiction occurs
Increase of Cortisol (stress hormone)
Increase of Vasopressin
Increases stress
Increases fear to lose
Increases jealousy
Increases attention
Increases susceptibility to painful stimuli
Makes female psychology more fragile, being
easily upset and sentimental
Increases attachment
Increases sexual arousal
Increases sexual attraction
Increases libido
Decreases anxiety
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Increase of Oxytocin
Increase of Norepinephrine
Increases euphoria
Increases motivation
Increases confidence
Attachment to the lover is increased
Increases happiness. A very happy mood
Increases libido
Increases pleasure taken from love making
Induces more intense and powerful orgasms
Increases empathy
Increases being romantic and sentimental
Decreases fear and anxiety
Increases attachment to life
Sympathetic Autonomous Nervous System is
activated
Increases excitation.
Increases heart beats and palpitations
Episodes of hypertension
Increases alertness
Increases pleasure
Increases libido
Increases joyful mood and happiness
May increase anxiety
Decreases sleep
References: Bartels, 2000-2004; Esch, 2005; Fisher, 2006-2010; Fxu, 2011; Kumsta, 2012; Marazziti, 1999-2003-2004-
2010 ; Martin, 2012; Ortigue, 2007-2010; Tarlaci, 2017; Zeki, 2007-2010; Fischetti, 2011; Diamond, 2012; Aron, 2005;
Sayin, 2017a-c, 2018a-c
Table-3: The Cortical and Limbic Brain Structures That are Activated During Orgasm
(human fMRI studies)
Areas Activated
During
Orgasm
Possible Function of the Brain Regions
Ventral Tegmental
Area
Pleasure-Reward circuitry ● Projections of many dopaminergic neurons to NA,
prefrontal cortex, cingulate, ventral pallidum ● Dopaminergic pleasure reaction
Nucleus
Accumbens
Release of dopamine ● sexual conditioning and learning ● Fantasy and variations ●
Remembering old events ● Association ● Imagination ● Novel sexual pleasure
objects ● pavlovian conditioning
Anterior Cingulate
Self-knowledge ● Subjective feelings ● Perception of the self ● Perception of
someone’s own pleasure
Insula
Emotion ● romantic feelings ● romantic love ● anger ● empathy ● pleasure and
happiness
Amygdala
Emotions ● sexual aggressiveness ● sympathetic physiological effects ● fantasy ●
game-role play ● increases heart beat and blood pressure
Hippocampus
3-D imagination ● Fantasy ● Sexual game-role play ● Memory ● Learned sexual
acts ● Pavlovian conditioning Emotions ●
Hypothalamus
increases heart beat and blood pressure ● sympathetic physiological effects
PVN-D4 receptors
Release of OXYTOCIN into pituitary and into the brain (CSF) ● OXYTOCIN triggers
both male ejaculation and female orgasm
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Figure-5: The Activated Areas during the Stimulation of Nipple, Clitoris, Vagina and Cervix. Published with the permission of Prof. Barry
Komisaruk. Reference: Komisaruk Barry R, N Wise, E Frangos, WC Liu, K Allen, S Brody. Women's clitoris, vagina, and
cervix mapped on the sensory cortex: fMRI evidence, Journal of Sexual Medicine; 8(10):2822-30, 2011. Published with the
permission of Prof. Barry Komisaruk.
Figure-6: Left: Regional Activation at orgasm compared with early stimulation. Regional brain activity during the 20 seconds at the
initiation of stimulation. Right: Regional activation at orgasm compared with recovery. Brain activity during 20 seconds immediately after
the button press, subtracted from 20 seconds of activity starting at the onset orgasm. Published with the permission of Prof. Barry
Komisaruk.
Reference: Wise NJ, Frangos E, Komisaruk BR. Brain activity Unique to Orgasm in Women: An fMRI Analysis. Journal of Sexual Medicine, 14 (11): 1380-1391;
2017. ● Jannini E.A, Wise N. Frangos E. and Komisaruk BR. Peripheral and Central Neural Bases of Orgasm. In Textbook of Sexual Function and Dysfunction:
Diagnosis and Treatment, First Edition, Edited by Sue W. Goldstein, Noel N. Kim, Anita H. Clayton. New York: John Wiley & Sons Ltd, 2018. Chapter 13,
pp:179-195; 2018.
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Figure-7: Regional Activation of Brain Regions (at fMRI) of Women in 10 seconds After the Start of Self -Induced Orgasm. The pleasure hot spots
of N. Accumbens, Amygdala, Hippocampus, Cingulate Cortex, Insula, Hypothalamic PVN area, and some other structures of limbic system were
activated with the start of orgasm. Published with the permission of Prof. Barry Komisaruk. Reference: Jannini E.A, Wise N. Frangos E. and
Komisaruk BR. Peripheral and Central Neural Bases of Orgasm. In Texbook of Sexual Function and Dysfunction: Diagnosis and Treatment, First Edition, Edited by Sue
W. Goldstein, Noel N. Kim, Anita H. Clayton. New York: John Wiley & Sons Ltd, 2018. Chapter 13, pp:179-195; 2018.
During orgasm, also, the amygdala,
hippocampus and hypothalamus are activated
in humans detected by fMRI. Amygdala is
correlated with emotions and innate
feelings, sexual aggressiveness, fantasy,
game or role play, creating new pleasure
objects. Hippocampus controls spatial and
3-D learning capabilities, visual learning,
memory, virtual mapping, and
imagination; during orgasm probably
activation of the hippocampus plays a role
in fantasy, imagination, remembering other
orgasms or learned sexual behavior.
Hypothalamus is another hedonic hot spot,
and also controls the basic physiological
conditions, such as heart beat, blood
pressure, etc. (Komisaruk, 2006; Jannini,
2018)
Another region which is activated
during, particularly, female orgasm is the
paraventricular nucleus of hypothalamus
(PVN). This is an area which has oxytocin
producing cells and oxytocin is released
from PVN and transmitted into the
posterior pituitary, where -during orgasm-
it is released into the bloodstream.
Oxytocin may be essential for the start of a
female orgasm, because it starts orgasmic
contractions in the uterus. PVN and
oxytocin may also play roles in male
erection and ejaculation, acting as
sympathetic preganglionic excitatory
neurotransmitter (Veronneau-Longueville,
1999; Jannini, 2018). Thus oxytocin plays
important triggering roles in both male
ejaculation and female orgasm. (Table-3)
Four Nerves Control
the Female Orgasm
Since Masters & Johnson, the
classical “orgasm triggering” organ was the
glans clitoris (Masters & Johnson, 1966).
However, other orgasm triggering
erogenous zones have been defined such
as, G-Spot, DVZ (Deep Vaginal Erogenous
Zones) (Sayin, 2012, 2015, 2017-a,b; Levin,
2006, 2014; Chua, 1997; Morris 2004).
Also many non-genital erogenous
zones and experiences have been described
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such as: zone orgasms (such as groin,
licked finger, earlobes, underarm), mouth
orgasms, anal orgasms, breast and nipple
orgasms, birth orgasms, phantom orgasms,
epileptic orgasms, and orgasmic cataplexy
(sudden focal or generalized muscle
weakness, usually, but not always,
associated with narcolepsy) (Komisaruk &
Whipple, 2012; Poryazova, 2009). There
should be neurophysiological explanations
to all of these phenomena.
Case studies of peri-orgasmic
phenomena have been reviewed, including
cases describing cataplexy (sudden
weakness), crying, dysorgasmia,
dysphoria, facial and/or ear pain, foot pain,
headache, pruritus, laughter, panic attacks,
“post-orgasm illness syndrome”, seizures,
and sneezing (Reinert & Simon, 2017). The
reported literature review confirmed the
existence of diverse and frequently
replicated peri-orgasmic phenomena.
These published observations carry the
value of generating hypotheses that can
promote further research on the
neurophysiologic mechanisms of orgasm
and its diverse multi-dimensional
experiences.
Conclusions:
In the 21st century, the existence of
the G-Spot and vaginal-coital orgasms is
still debated. Human beings are not cloned
prototypic creatures; there may be many
variations and differences between people.
G-Spot or DVZ may not be perceived in
every woman all the time, but this variance
does not exclude the possibility of the
existence of other “genital hot zones”.
DVZ was first defined by the
famous British zoologist Desmond Morris
(Morris, 2004); however, the pleasurable
sensitivity of anterior and posterior walls
of the vagina have been reported for a long
time by many researchers, since Sigmund
Freud (Reich, 1973; Singer, 1973; Fisher,
1972, 1973; Kaplan, 1981; Ladas, 1982;
Britten, 1983; Whipple, 1988; Bancroft,
1989; Escapa, 1989; Komisaruk, 2003, 2004,
2005, 2006; Zdrok, 2004; Carellas, 2007;
Sayin, 1993, 2012-a,b, 2014, 2015, 2017-a,b,
2018; Levin, 2006, 2014; Chua, 1997).
In vaginal-coital orgasms, there may
be more components to trigger an orgasm,
such as, DVZ areas with cervix and PFM or
other psychological input from the brain
itself. Other than clitoral orgasms and
vaginal orgasms; blended orgasms have
also been defined (Ladas, 1982; Levin, 2006,
2014, Sayin, 2012-a,b, 2017-a,b,c, 2018a,
2019).
Ladas hypothesized that the G-Spot
was responsible for the triggering
mechanisms of vaginal orgasms, while
vaginal orgasms were mediated through a
reflex arc through sacral plexus via the
pelvic nerve; clitoral orgasms were also
mediated through a similar pathway via
the pudental nerve. According to the
hypothesis defended in the book “G-Spot”,
blended orgasms were the unification of
two types of orgasms, i.e. vulva-uterine
orgasms, which were mediated through the
pudental, pelvic and hypogastric nerves
(Ladas, 2005-1982). If there are separate
vaginal orgasms mediated by some
different neural pathways other than
‘clitoral orgasm pathway’, then there
should be blended orgasms”, as well, which
may occur when both of those pathways
that mediate clitoral and vaginal orgasms
are activated at the same time.
According to the latest fMRI, PET,
evoked potential, and vibe stimulation
studies of various regions of the female
genitalia, it is conceptualized that there is
no single pathway that controls female
orgasm. At least we know that the
pudental, pelvic, hypogastric nerves and
vagus are involved in the development of
female orgasm (Komisaruk, 2006; Levin,
2006, 2014). The table below is a summary
of the pathways and routes which can
trigger female orgasms (Table-4):
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Table 4: Four Nerves and Many Different Pathways Control Female Orgasm & ESR Orgasms:
Glans clitoris Pudental N. Sacral plexus
BRAIN Clitoral orgasm
Parts of clitoral complex (crus, body, bulbus etc)
Pudental N. Sacral plexus BRAIN
Clitoral orgasm or Vaginal orgasm, or
contributes
Parts of clitoral complex (crus, body, bulbus etc)
Pelvic N. Sacral plexus BRAIN Vaginal
orgasm, or contributes
G-Spot Pelvic N. Sacral plexus BRAIN
Vaginal orgasm; and ejaculation in some women
Various vaginal stimulation during coitus
Pelvic N. Sacral plexus BRAIN Vaginal
orgasm
A-Spot Pelvic N. (possibly partially
hypogastric N.) Sacral plexus (+ partially Pelvic
plexus) BRAIN Vaginal orgasm, or
contributes to Vaginal orgasm
O-Spot Pelvic N. (possibly partially
hypogastric N.) Sacral plexus (+ partially Pelvic
plexus) BRAIN contributes to Vaginal
orgasm, Anal orgasm
PFM (PC-Muscle) Pelvic N. (possibly partially
hypogastric N.) Sacral plexus (+ partially Pelvic
plexus) BRAIN Vaginal orgasm, or
contributes to Vaginal orgasm
Cervix Partially Pelvic N. + Mostly Hypogastric N.
Pelvic Plexus (+ partially sacral plexus) BRAIN
Vaginal orgasm, or contributes to Vaginal orgasm
Cervix Vagus N. BRAIN Vaginal orgasm, or
contributes to Vaginal orgasm,
Uterus Hypogastric N. + Vagus N. Pelvic Plexus +
BRAIN contributes to Vaginal orgasm
Anus + Rectum Infra Anal N. + Pudental N. + Pelvic
N. + Anal sphincter nerves Sacral Plexus (BRAIN)
Anal orgasm (O-Spot stimulation contributes to
anal orgasms)
Nipples Intercostal N. Pituitary Oxytocin
Pathway BRAINNipple orgasm; or contributes to
Clitoral orgasm, Vaginal orgasm
BRAIN-imagination-fantasy-sexual images Pituitary
Oxytocin Pathway BRAIN Brain orgasm or
contributes to all kind of orgasms
Table-5: The Main Characteristics of Women with ESR and Expanded Orgasm Experience
The ESR women experienced vaginal,
clitoral and blended orgasms, as
described by Ladas et al.
ESR women described a phenomenon called G-
Spot orgasms and blended orgasms.
The ESR women experienced multiple
orgasms in most of their sexual activities
ESR women described sensitive erogenous zones
in their genitalia other than clitoris.
The ESR women were able to attain long
lasting and/or prolonged and/or multiple
and/or sustained orgasms and/or status
orgasmus that lasted longer than the
classical single orgasm and/or multiple
orgasm patterns defined in the literature.
The ESR women were measured to have strong
pelvic floor muscles (PFM) compared to NESR
women; Kegel Perineometer measurement
showed that their PC muscle strength was > 20
milibars.
ESR women admitted to have a form of
altered states of consciousness (ASC)
during some of their prolonged orgasms
and/or status orgasmus
ESR women masturbated more frequently
compared to NESR women. The average
masturbation frequency > 5 times per week.
The libido of ESR women was very high
compared to NESR women
ESR women had erotic fantasies more frequently
than the NESR women. > 5 times per week.
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Figure-8: Deep vaginal erogenous zones (DVZ).
A Form of Peak Experience: Expanded
Orgasms and ESR
Expanded Sexual Response
(ESR) is a recently defined phenomenon
(Rhodes, 1991; Taylor, 2000, 2002;
Armagan, 2012; Sayin, 2012a-b, 2013,
2014, 2015a-b, 2017-a,b,c, 2018-a,c, 2019).
ESR was defined as, “being able to attain
long lasting and/or prolonged and/or
multiple and/or sustained orgasms and/or
status orgasmus that last longer and are
more intense than the classical orgasm
patterns defined in the literature” (Sayin,
2010, 2011a-b-c, 2012a, 2013). The
duration of expanded orgasms (EO) and
ESR varied from woman to woman,
lasting from several minutes to tens of
minutes (Schwartz, 1999; Taylor, 2000,
2002; Sayin, 2010, 2012a-b, 2013). In the
literature, the highest number of
orgasms in a woman recorded by Dr.
William Hartman and Marilyn Fithian
was reported to be 134 per hour (Sayin,
2010, 2012a), this subject was probably
experiencing a form of status orgasmus.
During those cases no objective scientific
data such as EEG (in 1950s) were
recorded. Most of the fMRI and imaging
studies are about single female orgasms;
no EEG, PET, fMRI, MR studies have
been performed on the multiple
orgasms or ESR phenomenon yet.
Status orgasmus term is
generally mixed with status epilepticus!
Actually they are totally different
physiological conditions. Status
orgasmus was first coined by Masters &
Johnson after observing a female, who
had experienced an orgasm lasting for
43 seconds. (Masters & Johnson, 1966).
Some complex partial seizures, and focal
temporal lobe epilepsy cases that have
been associated with orgasms were
reported; namely, an epileptic seizure
resulted in orgasms (Chuang 2014, Luef
2008, Surbeck 2013, Arias 2019, Blumer
1970), as well as there are some cases in
which orgasms induced seizures
(Özkara 2006). Normally, it is reported
that temporal lobe epilepsy generally
induces hypo-sexuality (Demerdash
1991). Sexual arousal can also happen
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during some epileptic auroras (Surbeck,
2013).
Although a small proportion of
women has attained or can attain ESR to
date, ESR is a learned peak experience
phenomenon that can be developed in
some women (an estimate of 10-12 % of
female population) by training and
education. To determine the main
parameters and mechanisms of ESR, we
investigated the main characteristics of
women who have developed ESR (Taylor,
2000, 2002; Armagan, 2012; Sayin, 2012a-b,
2014, 2015-a,b, 2017-a,b,c, 2019) (Table-5):
Conclusion: The alterations of
hormones and/or neurotransmitters
during, particularly, female orgasm, and
sexual activity are summarized in this
article, as well as the activated brain areas
during sexual stimulation, arousal and
orgasm. Female orgasm is also a further
form of ordinary liking and pleasure. There
are no imaging studies related to
consecutive multiple orgasms, expanded
orgasms or ESR yet; we do not know what
happens in the brain if a woman attains
continuous orgasms for a couple of
minutes. However, citing the subjective
descriptions of women about their
prolonged orgasms (Taylor, 2000, 2002;
Sayin, 2012-a,b, 2015-a,b, 2017-a,b,c,
2018a,c), it is very obvious that these
orgasmic experiences are a form of “peak
experience”, which will hopefully be
investigated and illuminated in the coming
years.
Figure-9: Extended or expanded orgasm
patterns in ESR women.
In most of the researches single female orgasm
has been investigated thoroughly. As a matter of
fact, women have the capacity to experience many
orgasms successively, unlike men. ESR orgasms can
be attained in some women (10-12 %) by education
and training; actually what is taught in Tantra
workshops or Tantra training is to learn ESR
orgasms. The type of ESR orgasms may vary. Some
successive multiple orgasms may continue from a
couple of minutes to tens of minutes. In the plots
blended orgasms, which are the unification of
clitoral and vaginal orgasm reflexes are shown with
multiple peaks as a depiction. In ESR orgasms many
small or large orgasm patterns may occur
successively. There may be some periods of
cessation while the orgasm trains continue. In
status orgasmus orgasmic contractions and trains
continue; such that one orgasm ends, the other one
starts. A general pattern of status orgasmus is a
couple of minutes; however, among around 160
ESR women we have investigated, some women
mentioned about orgasms lasting 5 to 15 minutes,
with a last very intense and powerful orgasm at the
end (Big-O).
SexuS Journal www.sexusjournal.com Winter-2019 │Volume: 04 │Issue: 11 │Pages: 907-946
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NEUROCHEMISTRY OF DESIRE, AROUSAL AND PLEASURE
Summary of the Role of Neurotransmitters in Desire, Pleasure and Orgasm
Table-6 : Correlation of Neurotransmitters and Sexual Behavior; Desire, Arousal, Orgasm
MALES
Change in Sexual
Function
FEMALES
Change in Sexual
Function
Dopamine
↑↑↑
↓↓↓
Dopamine
↑↑↑
↓↓↓
Sexual Desire
↑↑
Sexual Desire
↑↑↑
Sexual Arousal
Sexual Arousal
↑↑
Orgasm
↑↑
Orgasm
↑↑↑
↓↓
Norepinephrine
↑↑↑
↓↓↓
Norepinephrine
↑↑↑
↓↓↓
Sexual Desire
Sexual Desire
Sexual Arousal
Sexual Arousal
Orgasm
Orgasm
Serotonin
↑↑↑
↓↓↓
Serotonin
↑↑↑
↓↓↓
Sexual Desire
?
Sexual Desire
Sexual Arousal
?
Sexual Arousal
Orgasm
delayed
Orgasm
↓↓ - Ø
↑↑
Acetylcholine
↑↑↑
↓↓↓
Acetylcholine
↑↑↑
↓↓↓
Sexual Desire
Sexual Desire
Sexual Arousal
Sexual Arousal
?
?
Orgasm
Orgasm
↓↑
?
Oxytocin
↑↑↑
↓↓↓
Oxytocin
↑↑↑
↓↓↓
Sexual Desire
Sexual Desire
Sexual Arousal
Sexual Arousal
Orgasm
Orgasm
↑↑↑
Histamine
↑↑↑
↓↓↓
Histamine
↑↑↑
↓↓↓
Sexual Desire
Sexual Desire
?
Adrenaline
↑↑↑
↓↓↓
Adrenaline
↑↑↑
↓↓↓
Sexual Desire
?
Sexual Desire
Sexual Arousal
?
Sexual Arousal
Orgasm
Premature
Orgasm
↑↑
↑↑?
Opioids
↑↑↑
↓↓↓
Opioids
↑↑↑
↓↓↓
Desire-Arousal
↑?
Desire-Arousal
↑?
Orgasm
↓↑
↑?
Orgasm
↓↑
↑?
References: Komisaruk, 2006; Meston, 2000; Kim, 2015; Bancroft, 2005; Pfaus, 2009, 2012; Ahlenius, 1991;
Hull, 2011; Adams, 2012; Delgado2005; Meston, 1999; Feiger, 1996; Paterson, 1993; Montejo-Gonzalez,
1997; Landen et al., 2005; Robinson, 2000; Melis, 1995, Brunton, 2011; Sayin, 2019
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Dopamine
Dopamine is the major “pleasure and
reward neurotransmitter in the limbic
circuitry. As a general action, dopamine
and increased dopaminergic transmission:
Increases sexual motivation
Increases sexual desire
Increases pleasure in both sexes
Increases libido
Enhances female orgasms; in some
cases prolongs female orgasms.
Facilitates ejaculation in males
D1-like dopamine receptors (D1 and
D5) are excitatory by increasing cAMP-,
while D2-like dopamine receptors are
inhibitoryby decreasing cAMP-. It is
reported that dopaminergic neural
pathways originating from VTA play
important roles in the occurrence of
pleasure, reward perception, sexual
hedonism and orgasm in animals and
humans. The drugs that elevate dopamine
levels in the limbic system (such as
amphetamines, L-DOPA); various D-1
receptor agonists (like apomorphine) also
increase sexual activity, libido, and
pleasure and enhance orgasm. Anti-
parkinsonian therapy with L-DOPA may
induce hypersexuality, due to the increased
dopamine levels in the brain (Corty, 1997;
Uitti, 1989; Meston, 2000).
There are some reports indicating
the parkinsonian medication, L-DOPA
produces erection and improves sexual
activity and enhances orgasms in humans
(Bowers, 1971; Hyyppa, 1970). Also,
dopaminergic receptor agonist therapy of
Parkinson disease and Restless Legs
Syndrome can cause the unwanted side
effect of inappropriate hypersexuality (and
other impulse control disorders, such as
pathological gambling, compulsive eating,
and compulsive shopping) with negative
consequences (Moore, 2014; Lopez, 2017).
The D1 and D2 dopamine agonist,
apomorphine facilitates erection in normal
men (Danjou, 1988; Lal, 1984), while anti-
psychotic medication, which blocks D-1
receptors, also decrease motivation,
pleasure and sexual activity (Aizenberg,
1995; Marder, 1994).
Extensive animal studies by Pfaus et
al. showed that anticipatory excitement can
be increased by treatments that increase the
incentive salience of the sex partner and by
dopamine agonist drugs (Pfaus, 2009,
2012). These effects may be reduced by
microinjections of dopamine antagonists in
the nucleus accumbens (NA), - a hedonic
hot spot-, and some other pleasure spots
(Pfaus, 2009).
Animal studies (mostly rats) have
uncovered the fact that certain brain
structures regulate sexual activity by
means of dopaminergic transmission
.
The
mixed D1-D2 agonist
apomorphine,
when infused into
the
medial preoptic
area of the
forebrain,
increased the
number
of ejaculations
and the r at i o
of rats that
copulated. Dopamine
receptor antag oni st s (li ke
ha lop erido l)
produced
the opposite
effect when infused into the medial
preoptic
area, namely it decreased the
number of
intromissions
and
ejaculations
(Melis, 1995). There are
many other findings from animal and
human studies which emphasize the
enhancing role of dopamine in
motivation, desire, pleasure and orgasm
(Kim, 2015; Meston, 2000; Komisaruk,
2006).
Today, it is an established fact that,
after 50 years of animal
neuropharmacology, microdialysis,
micro-injection, drug dependence and
behavior studies, as well as many clinical
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human drug, medication and addiction
studies, dopamine is believed to be the
major neurotransmitter of desire, pleasure,
motivation in the brain, while it is also
released during intense pleasure, love,
ecstasy, joyful states of mind, as well as
during various orgasm experiences in
humans (Kim, 2015; Komisaruk, 2006;
Jannini, 2018; Pfaus, 2012, Tarlaci, 2017).
(Fig-10)
Norepinephrine
Adrenaline (epinephrine) and
noradrenaline (norepinephrine), having
very similar molecular structures, are the
mediators of the sympathetic autonomous
nervous system. Adrenaline is secreted
from adrenal glands (on kidneys) into the
bloodstream. Norepinephrine is a
neurotransmitter in the brain. The cell
bodies of adrenergic neurons originate
from the locus ceruleus at the midbrain,
projecting into the limbic system, motor
cortex, prefrontal cortex, sensory-motor
cortex, hypothalamus and limbic
structures. Norepinephrine binds to two
classes of receptors, coined as “α” and “β”.
Alpha receptors when stimulated by
norepinephrine or adrenaline inhibit
adenylate cyclase activity. Beta receptors,
when stimulated by those agonists,
stimulate second messenger adenylate
cyclase activity. Alpha-1 receptors are post-
synaptic; Alpha-2 receptors are pre-
synaptic auto-receptors, which control the
release of neurotransmitters, as a feed-back
mechanism. Drugs, such as Yohimbin or
clonidine, bind to alpha-2 receptors and
decrease the release of norepinephrine,
thus the sympathetic tone is decreased, and
sedation may occur (Brunton, 2011).
Many animal studies showed that
release of norepinephrine and increased
norepinephrine transmission results in
increased sexual activity (Kim, 2015).
Ephedrine (alpha-1 agonist) has
been shown to significantly increase
vaginal pulse amplitude responses to an
erotic videotape. Clonidine, an
antihypertensive medicine and an alpha-2
auto receptor agonist, decreased vaginal
pulse amplitude responses to erotic stimuli.
Sympathetic activation increased vaginal
blood volume responses to erotic stimuli in
sexually active women and hypo sexual
women. Anorgasmic women exerted an
inhibition in physiological sexual arousal
under conditions of sympathetic activation.
These clinical studies clearly showed that
activation of the sympathetic nervous
system enhances arousal and desire
(Meston, 1995, 1996, 1997, 1998; Kim, 2015).
As a general action, an increase in
norepinephrine and adrenergic
transmission,
increases sexual motivation and
libido
increases pleasure
facilitates female orgasms
facilitates ejaculation, may induce
premature ejaculation in males
enhances orgasms and orgasmic
pleasure
dopaminergic transmission works
parallel with dopaminergic
transmission, but with opposite
direction that of serotonin.
Serotonin
In sexual behavior, generally
serotonin and dopamine work in opposite
directions from each other. Serotonin is
well known in:
Decreasing libido (in both males &
females)
Reducing sexual pleasure (in both
sexes)
Reducing and/or blocking female
orgasm
Delaying male ejaculation
(particularly Lustral, which is used
in the treatment of premature
ejaculation)
Various inhibiting effects on sex
behavior
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Drugs that decrease serotonin
facilitate sexual behavior in animal
experiments; however, drugs such as SSRI
antidepressants, which increase serotonin
levels or serotonin itself directly
microinjected into the rat brain, inhibit
sexual motivation and ejaculation in male
rats (Komisaruk, 2006). Stimulation of
(presynaptic, inhibitory autoreceptors)
serotonin 1A receptors in testosterone-
treated male rats (by specific agonists
such as 5-HT-1A agonist, 8-OH- DPAT)
facilitated ejaculation by inhibiting
release of serotonin into the synapses
(Ahlenius, 1991).
Serotonin in the lateral
hypothalamus inhibited sexual behavior by
inhibiting orexin neurons, which normally
stimulates neurons in the
mesocorticolimbic dopamine tract
(Hull, 2011). In female rats, SSRI-treated
females had sexual dysfunction such
as increased escape behavior and
decreased active investigation of the male
(Adams, 2012)
In clinical human trials, SSRI
antagonists also decrease libido, sexual
desire, and diminish or totally block the
development or intensity of female
orgasms (Komisaruk, 2006; Kim, 2015;
Meston, 2000). Between, 2 % to 75 % of
patients using SSRI anti-depressants
reported the inhibiting and decreasing
side effects of sexual behavior,
particularly decreasing pleasure,
satisfaction and blocking female orgasm
(Delgado 2005; Meston, 1999; Feiger, 1996;
Paterson, 1993; Montejo-Gonzalez, 1997).
In human studies, 41% of patients who
were using SSRIs reported sexual
dysfunction such as decreased desire,
orgasmic problems, or premature
ejaculation (Landen et al., 2005).
Beta-Endorphin
It has long been known that
there is much evidence of the negative
effects of exogenous opiates, such as
morphine and heroin, on the sexuality
of male and female drug addicts,
reducing sexual interest, impairing
genital response and blocking
ejaculation and orgasm. This sexual
dysfunction may or may not be
reversed after treatment or opiate
withdrawal (Pfaus, 1987). Exogenous
opiates may be inducing intense
pleasure followed by a sedative and
calm episode, by means of activation of
meso-limbic dopaminergic system
(Robinson, 2000). In women
masturbating to orgasm, naloxone, an
opiate antagonist, enhanced the
pleasure during orgasm in low doses,
but reduced the arousal and orgasmic
pleasure in high doses (Gillman, 1983).
Endogenous opiates may have both
inhibitory and facilitator effects on
various sexual functions. (Figs-10-11)
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Figure-10: Molecular structures of some
neurotransmitters or hormones which are important
in the development of pleasure response. As seen,
some of the structures are very similar to each
other, as in dopamine, norepinephrine, epinephrine,
serotonin and GABA.
Summary of the Role of Hormones in Desire, Pleasure and Orgasm
Table-7 : Correlation of Hormones and Sexual Behavior; Desire, Arousal, Orgasm
MALES
Change in Sexual
Function
FEMALES
Change in Sexual
Function
Testosterone
↑↑↑
↓↓↓
Testosterone
↑↑↑
↓↓↓
Sexual Desire
Sexual Desire
Sexual Arousal
Sexual Arousal
↑↑↑
Orgasm
Orgasm
↑↑
Estrogen
↑↑↑
↓↓↓
Estrogen
↑↑↑
↓↓↓
Sexual Desire
?
?
Sexual Desire
↑?
Sexual Arousal
?
Sexual Arousal
?
Orgasm
?
?
Orgasm
↓↑?
?
Progesterone
↑↑↑
↓↓↓
Progesterone
↑↑↑
↓↓↓
Sexual Desire
?
Sexual Desire
Sexual Arousal
?
Sexual Arousal
Orgasm
?
?
Orgasm
Prolactin
↑↑↑
↓↓↓
Prolactin
↑↑↑
↓↓↓
Sexual Desire
Sexual Desire
Sexual Arousal
Sexual Arousal
?
?
Orgasm
?
Orgasm
Oxytocin
↑↑↑
↓↓↓
Oxytocin
↑↑↑
↓↓↓
Sexual Desire
Sexual Desire
Sexual Arousal
Sexual Arousal
↑↑
Orgasm
Orgasm
↑↑↑
Pheromones
↑↑↑
↓↓↓
Pheromones
↑↑↑
↓↓↓
Sexual
Attractiveness
↓?
Sexual
Attractiveness
↑?
?
SHBG
↑↑↑
↓↓↓
SHBG
↑↑↑
↓↓↓
Sexual Desire
Sexual Desire
Sexual Arousal
Sexual Arousal
Orgasm
Orgasm
Cortisol
↑↑↑
↓↓↓
Cortisol
↑↑↑
↓↓↓
Sexual Desire
Sexual Desire
Sexual Arousal
Sexual Arousal
References: Komisaruk, 2006; Meston, 2000; Kim, 2015; Bancroft, 2005; Pfaus, 2009, 2012;
Ahlenius, 1991; Hull, 2011; Adams, 2012; Delgado2005; Meston, 1999; Feiger, 1996;
Paterson, 1993; Montejo-Gonzalez, 1997; Landen et al., 2005; Robinson, 2000; Melis, 1995,
Brunton, 2011; Katzung, 2012
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Figure-11: The structure of basic sex hormones and the reaction pathways through which they are
synthesized from cholesterol. Some of the testosterone in women can easily turn into Oestradiol.
Testosterone
Testosterone is the major sex
hormone in males, which affects many
aspects of sexual behavior. Testosterone is
synthesized mostly in Leydig cells of the
testes, adrenal glands and fat adipose
tissue. Although the major female sex
hormone estrogen influences femininity
and contributes to sexual behavior
positively (see below), testosterone also
induces sexual aggressiveness and takes
important roles in the formation of libido
in women. In women, testosterone is
synthesized in the adrenal glands and
adipose fat tissue (Katzung, 2012;
Komisaruk, 2006; Hertlein, 2009). As a
general finding;
Testosterone increases libido in
both sexes
Blood free testosterone levels
(which is not bound to SBHB)
determines the frequency and
duration of sexual activity in men;
increased testosterone levels
shorten refractory period, prolongs
erection and increase the number
and volume of emissions
Blood free testosterone levels
enhance pleasure, desire and
orgasm in women
Increased testosterone plays
important roles in the production
spermatozoon in testicles, healthy
and active sperm count
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In adolescent boys, levels of free
testosterone were shown to predict the
frequency of sexual thoughts and monthly
measures of salivary testosterone have
been positively correlated with the
initiation and rate of sexual intercourse
(Halpern 1994, 1998; Udry, 1985).
Testosterone administration is reported to
enhance libido and sexual activity in aging
males and anorgasmic women (Flynn,
MA; Komisaruk, 2006; Kaplan, 1974;
Meston, 2000; Hertlein, 2009; Kim, 2015).
It was also found that sexual
desire, arousal and fantasies in the women
whose ovaries were dissected were very
high compared with the ones having a
high SHBG (sex hormone binding
globulin) versus low SHBG blood levels;
the women with lower SHBG levels were
more sexually active (Sherwin, 1987).
It is important to keep in mind that
free testosterone or estradiol levels of
blood are more crucial than the total
hormone levels. The drugs or events that
increase SHBG levels, decrease libido,
desire and orgasmic pleasure, since the sex
hormones binding to SHBG are readily
cleared from blood and metabolized,
particularly testosterone and oestradiol.
For instance, many of the oral
contraceptives increase SHBG in women’s
blood, decreasing free serum testosterone
and estradiol levels, which results in
decreases libido, diminished sexual
activity and less powerful orgasms
(Brunton, 2011).
Some other researchers have
found that there is significant relationship
with the female’s testosterone levels and
initiation of coitus and sexual activity;
also, it is found that higher levels of
vaginal blood flow responses existed as a
response to erotic stimuli among women
with high vs lower levels of blood
testosterone (Halperne, 1997; Schreiner-
Engel, 1982). Some other studies also
confirmed that testosterone administration
to normal women increased desire and
arousal towards sexual activity and erotic
stimuli (Bancroft, 2005). (Fig-11)
Estrogen (Oestradiol)
Estrogen have been found not to have
very significant effects on sexual desire in
males or females (Meston, 2000), although
it has influence on femininity and
feminine psychology. In women, as cited
above, free testosterone levels affect libido
and sexual aggressiveness, much more
than estrogen does, while estrogen
contributes to vaginal lubrication.
Oestradiol increases
norepinephrine synthesis in the brains of
female rats (Ramírez and Carrer, 1982).
Progestorone
Progesterone was shown to
decrease sexual activity, libido, and
progesterone treatment was successful to
reduce the excessive sexual desire in men.
Some contraceptives were also shown to
exert a desire and sexual interest
diminishing effects on women (Meston,
2000).
Prolactin
Prolactin is secreted from pituitary
after the orgasm of both sexes and it is
thought that it is responsible of the dizzy
and drunkenness-like symptoms after
orgasm, along with endorphins. When
prolactin is released, testosteron levels of
males drop, inducing a refractory period;
this may not happen in women as
profound as men. It has been shown that
prolactin decreases libido and sexual
interest in males (Meston, 2000; Sayin,
2014, 2017a,b).
Prolactin is also regarded as satiety
hormone for sexual satisfaction (Brody,
2006, 2010); the more the prolactin levels
in the blood are, the less sexual interest
men have. 2 fold increase in the prolactin
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levels, which remained elevated for 1 h, in
women after sexual arousal (Exton, 1999).
Erectile dysfunction has been described in
men with abnormally high levels of
prolactin (Meston, 2000).
Oxytocin
Oxytocin (OXT) is a very
important hormone and neurotransmitter
that plays crucial roles in maternal
behavior, lactation mood and depression,
partner bonding, attachment, sexual
activity and orgasm (Viero, 2010; Meston,
2000; Argiolas, 1999; Kim, 2015; Crespi,
2015, Sayin, 2012a, 2014, 2017a, 2019) :
Lactation
Motherhood
Bonding and attachment
Passionate love
Birth (during parturition)
Mood and emotion
Sexual behavior in both sexes
Female orgasm
Male erection and ejaculation
Smooth muscle and uterus contraction
Complex emotions such as empathy,
liking, feeling warmth
Inflammation and immune response
Analgesia
OXT is produced by the supraoptic
magnocellular neurons of the
paraventricular nucleus (PVN) of the
hypothalamus, which project axons into
the posterior pituitary and thence into the
peripheral circulation (Kupfermann 1991).
OXT has also been proposed as a crucial
factor in partnership behavior (Insel
1992). Objective and scientific evidence for
OXT becoming important in sexuality
emerged during last three decades.
Sophisticated studies such as fMRI, show
that during sexual arousal and orgasm of
women, PVN regions are also activated
(Jannini, 2018; Komisaruk, 2011, 2006;
Wise, 2017) (See Figs, 5, 6, 7).
OXT receptors in the brain are widely
distributed, however they are very dense
at the regions: ventromedial nucleus of
hypothalamus, amygdala, septum, anterior,
olfactory nucleus, preoptic area, VTA,
hippocampus (Viero, 2010; Febo, 2009;
Young, 2009). Density of OXT receptors
also includes some of the reward-pleasure
regions, hinting that OXT may have direct
actions on pleasure-reward and sexual
response mechanisms, independent of
impact of dopamine or testosterone.
In animal studies, OXT administered
into CSF induced erection, probably a
testosterone dependent effect, which could
be prevented by OXT antagonists
(Argiolas, 1999). Dopamine agonists
enhance sexual response of the rats by
means of increasing OXT transmission;
because the increased sexual activity by
dopamine agonists, were reversed by OXT
antagonists (Argiolas, 1999). Systemic
administration of oxytocin facilitates
ejaculation in male rats treated chronically
with fluoxetine (Cantor 1999; de Jong
et al., 2007). Infusion of oxytocin
receptor antagonists block partner-
bonding.
Some researchers investigated the
interaction of OXT and serotonin in
animals. Fluoxetine, selective serotonin re-
uptake inhibitor, impaired ejaculation in
rats, which is reversed by OXT
administration (Cantor, 1999). It was
hypothesized that serotonin suppressed
ejaculation by blocking the actions of OXT.
Stimulation of D2 receptors in the
paraventricular nucleus of the
hypothalamus stimulates OXT release and
increases extracellular dopamine levels in
the NA (Succu et al., 2007), suggesting a
mechanism of dopamine and OXT
working in parallel by which
hypothalamic dopamine could integrate
with mesolimbic dopamine through an
oxytocin modulation or intermediary
action.
OXT induces penile erection and
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increases dopamine concentration in the
NA in rats. OXT-induced penile erection is
mediated by the firing of GLU neurons
projecting into the VTA (Succu et al., 2011).
OXT also induced penile erection when
injected into the paraventricular nucleus of
the hypothalamus, region CA1 of the
hippocampus, VTA and amgydala (Melis
et al., 2011).
Pioneering researchers of OXT had
found that plasma OXT concentration
increased around the time of orgasm in
men and women, remaining high for at
least 5 min after orgasm (Carmichael,
1987, 1994; Murphy, 1987). Carmichael et
al. reported a positive correlation between
oxytocin levels and the intensity of
orgasmic contractions in males and
females. Another study on women
showed that OXT in plasma increased in 1
minute after orgasm lasting for 5 minutes
(Blaicher, 1999). In this study, serum levels
of OXT in women increased, before and
after sexual stimulation, suggesting OXT
serves an important role in sexual arousal.
This study found genital tract stimulation
resulted in increased OXT immediately
after orgasm It should not be forgotten
that there are abundant enzymes which
degrade OXT in the blood and tissues, so
OXT cannot stay in the bloodstream for a
long time; however in the brain, as a
neurotransmitter its effects should be
regarded much longer than a couple
minutes. For multi-orgasmic women,
oxytocin increase was also found to be
correlated positively with subjective
reports of orgasm intensity. In a few case
reports synthetic form of oxytocin used to
facilitate breastfeeding was linked to
increased sexual desire and vaginal
lubrication (Anderson-Hunt, 1994, 1995).
Another study reported increases of
oxytocin during sexual arousal could be in
response to nipple/areola, genital, and/or
genital tract stimulation as confirmed in
other mammals (Anderson-Hunt, 1995).
Other studies also showed that there was
an increase in plasma OXT concentration
during petting, making love and orgasm
(Murphy, 1987; Krüger, 2003). Some of the
other behavioral and pharmacological
effects of OXT are summarized in Table-8.
Social Aspects
It is also hypothesized that OXT plays
important roles in social interaction,
emotional intelligence (EQ), empathy and
relationships with other people (Crespi,
2015). However, when some social
psychometric tests are performed, it is
proposed, unlike in sexual behavior, OXT
may have some contrary behavioral effects
compared to testosterone (Table-9),
hinting that OXT is more likely a feminine
and motherly hormone. Testosterone does
not only enhance sexual aggression,
however, but also aggression towards the
outer world and people, probably some
specific stimulating effects at amygdala,
while OXT decreases aggression and
fearful reactions (Guzmán , 2013; Kirsch P,
2005; Vitalo, 2009; Huber 2005; Guzmán
2013; Marazziti 2006; Heinrichs 2003;
Marazziti 2006). (Fig-11; Table-8)
The Phenomenon of Pleasure with
Sexsomnia and Epileptic Sexsomnia
The first classification of the
complex set of relationships between sleep
and sex—two fundamental “instinctual
drives” that can become pathologically
intertwined--was published in 2007
(Schenck et al.). Thirty-one published
cases were reviewed involving
“Sexsomnia” (also called “Sleepsex” and
“Sleep Related Abnormal Sexual
Behaviors”), which is a parasomnia, viz.
sleep behavioral and experiential disorder
(American Academy of Sleep Medicine
2014). Although various negative
consequences involving sexsomnia were
identified, including sexual assault of bed
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partners and negative psychosocial
consequences for patients and bed
partners, in four cases pleasurable aspects
of the sleep-sex were reported by the bed
partners. One woman commented in a
positive manner that her boyfriend’s
sleep-sex was more “aggressive and
dominant” than his waking sexual
behavior, and she “found some aspects of
the sleep-sex pleasurable…and a little
kinky,” such as “forceful albeit playful
biting and “talking dirty.” In fact, she
requested that her partner incorporate
some of the sleep sexual behaviors into
their wakeful daytime lovemaking.
Another woman commented on how her
boyfriend was a “different person during
these activitieshe is a more amorous and
gentle lover and more oriented toward
satisfying his partner when he is asleep.”
And a wife reported that her husband
would initiate sex in his sleep, when he
would be “more aggressive and more
amorous” compared to when he was
awake and having more passive sex with
her.
Video-polysomnography generally
identified parasomnia behaviors
(including sexual behaviors) emerging
from slow-wave (delta) sleep, as a classic
manifestation of a disorder of Non-REM
sleep arousal, as also found with
Somnambulism and Pavor Nocturnus
(American Academy of Sleep Medicine
2014). The brainstem monoamine
neurotransmitters serotonin (5-
hydroxytryptamine), localized in the
serotoninergic neurons of the dorsal raphe
nuclei, and norepinephrine, localized in
the noradrenergic neurons of the locus
ceruleus, are responsible for induction of
slow-wave sleep, in contrast to
acetylcholine (Ach) being responsible for
REM sleep induction.
In a variant of Sexsomnia called
Epileptic Sexsomnia, i.e. sexual seizures
during sleep, which was reviewed in the
above report (Schenck et al. 2007), in four
epilepsy cases, pleasurable aspects of sleep
related sexual seizures were reported by
the three patients and one bed partner. A
41-year-old woman with nocturnal
somatosensory seizures would experience
pleasurable (or painful) orgasms together
with vaginal dilatation during her
seizures. A 31-year-old man with
temporal lobe epilepsy would experience a
sleep related “sensory phenomenon along
with the twitching [that] was described as
‘being just like an orgasm…sexual and
intensely pleasurable,” but without
ejaculation being achieved. A 32-year-old
woman with an 18-year history of complex
partial seizures developed sleep related
hypersexuality arising from sleep that
began 3 weeks after surgery. “She would
wake in the middle of the night with
intense sexual desire and rouse her
husband. She stated a wish for her
husband to have the same operation.” In
another case, “a wife had started to look
forward to this happening,” referring to
her husband’s post-ictal (psychomotor
attacks) hypersexuality that occasionally
emerged from sleep.
Finally, it should be emphasized
that in the sexual parasomnia and epilepsy
cases just described, psychopathology was
uncommonly present and was not an
identified contributing factor to the
abnormal sleep related sexual behaviors
and experiences. Moreover, neither sexual
deprivation nor a previous history of
paraphilia or criminal sexual misconduct
was reported.
Acknowledgements: We thank Prof. Carl
Ruck from Boston University for reading the
manuscript and giving his valuable
comments and Prof. Barry Komisaruk
from Rutgers University for allowing his
fMRI images to be used. This review
article is supported by BAP (İstanbul
University-Cerrahpaşa) and CİSEATED-
ASERHERT funds.
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TABLE-8: SUMMARY OF VARIOUS OTHER BEHAVIORAL EFFECTS OF OXYTOCIN IN ANIMALS AND HUMANS
Classification
Physiological, Behavioral and Pharmacological Effects of Oxytocin
Reference
Maternal
Behavior
Female rats given OXT antagonists after giving birth do not exhibit typical maternal behavior.
van Leengoed
1987.
Virgin female sheep show maternal behavior toward foreign lambs upon cerebrospinal fluid infusion
of OXT.
Kendrick KM,
2004.
Fear and
anxiety
There is consensus that OXT modulates fear and anxiety.
Guzmán , 2013.
Nasally administered OXT was reported to reduce fear, possibly by inhibiting the amygdala.
Kirsch P, 2005.
In mice, an anxiolytic effect of OXT via the direct activation of the OXT receptors has been
demonstrated
Vitalo, 2009
Research showed that in rodents OXT can efficiently inhibit fear responses by activating an inhibitory
circuit within the amygdala.
Huber 2005.
OXT enhances the aversive social memory, leading the rat to display a greater fear response when
the aversive stimulus is encountered again.
Guzmán 2013.
OXT evokes feelings of contentment, reductions in anxiety, and feelings of calmness and security
when in the company of the mate
Marazziti 2006.
OXT may be important for the inhibition of the brain regions associated with behavioral control, fear,
and anxiety, thus allowing orgasm to occur. Research has also demonstrated that OXT can decrease
anxiety and protect against stress.
Heinrichs 2003.
OXT evokes feelings of contentment, reductions in anxiety, and feelings of calmness and security
when in the company of the mate.
Marazziti 2006.
Mood and
depression
OXT produces antidepressant-like effects in animal models of depression.
Matsuzaki 2012.
OXT may play a role and a deficit of OXT may be involved in the pathophysiology of depression..
McQuaid 2014
The antidepressant-like effects of OXT are not blocked by an OXT-R antagonist, hinting that these
effects are not mediated by the OXT-R.
Acevedo, 2015
Romantic
attachment
In some studies, high levels of plasma OXT have been correlated with romantic attachment. For
example, if a couple is separated for a long period of time, anxiety can increase due to the lack of
physical affection. OXT may aid romantically attached couples by decreasing their feelings of anxiety
when they are separated.
Marazziti D 2006
OXT may be important for the inhibition of the brain regions associated with behavioral control, fear,
and anxiety, thus allowing orgasm to occur. Research has also demonstrated that OXT can decrease
anxiety and protect against stress, particularly in combination with social support.
Heinrichs M, 2003
Thrust
A recent study demonstrated that a nasal spray of OXT raised the trust (in a stranger) of people
playing a money game.
Kosfeld, 2005.
Sex differences
It is shown that OXT differentially affects males and females. Females who are administered OXT
were faster in responding to social stimuli than males who received OXT.
Lischke A, 2012.
Estrogen has been shown to stimulate the release of OXT from the hypothalamus and promote
receptor binding in the amygdala
Lischke A, 2012.
Pets
In a 2003 study, both humans and dog OXT levels in the blood rose after five to 24 minutes of a
petting session.
Odendaal JS,
2003.
Immune
System
Inflammation
OXT is also thought to modulate inflammation by decreasing certain cytokines. Thus, the increased
release in OXT has the potential to improve wound healing, this anti-inlammatory effect could be due
to OXT reducing inflammation, thus allowing the wound to heal more quickly.
Gouin JP, 2010
Social
Interaction
According to a study published in 2014, silencing of OXT receptor interneurons in the medial
prefrontal cortex (mPFC) of female mice resulted in loss of social interest in male mice during the
sexually receptive phase of the estrous cycle.
Nakajima M, 2014
Analgesic Effect
The antinociceptive effect of OXT injected intrathecally was also reported in humans.
Yang, 1994
Several initial behavioral investigations speculated on the possibility of intrathecally administered
OXT exerting antinociceptive effects in a dose-dependent manner.
Lundeberg, 1993;
Xu, 1994; Yang,
2007
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A Multidisciplinary Academic Journal Published Quarterly by CİSEATED-ASEHERT www.ciseated.org www.sexusjournal.com 937
Table-9: PARALEL OR CONTRARY BEHAVIORAL EFFECTS OF OXTTOCIN AND TESTOSTERONE
Activity or Behavior
Oxytocin Effect
Testosterone Effect
Non-Parallel Effects-Social Behavior
Trust
↑↑↑↑
↓↓
Paternal Care
↑↑↑↑
↓↓
Performance on Reading
Mind in the Eyes Test
↑↑↑↑
↓↓
Visual-spatial Abilities
↓↓
↑↑↑↑
Attention to Angry Faces
↓↓
↑↑↑↑
Non-Defensive Aggression
↓↓
↑↑↑↑
Amygdala Activation
↓↓
↑↑↑↑
Amygdala Connectivity
with Cortex
↑↑↑↑
↓↓
Inducing aggression
↓↓
↑↑↑↑
Sensitivity to biological
motion
↑↑↑↑
↓↓
Parallel Effects-Sexual Behavior
Sexual Arousal
↑↑↑
↑↑↑
Libido
↑↑↑
↑↑↑
Enhancing Pleasure
↑↑↑
↑↑↑
Enhancing Orgasms
↑↑↑↑↑
↑↑
Sexual Aggression
↑↓
↑↑↑
Modified from: Crespi BJ, 2015. References: Carmichael, 1987, 1994; Murphy, 1987; Crespi, 2015; Argiolas, 1999; Sayin, 2012-a,b,
2014, 2015-a,b, 2017-a,b,c, 2018-a; Komisaruk, 2006; Jannini, 2018; Carmichael, 1987, 1994; Meston, 2000
Note: Figures, pictures, cartoons and diagrams are modified, drawn and created by Dr. Ümit Sayin using
Photoshop, Corel Draw and Powerpoint.
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