ArticlePDF Available

Abstract and Figures

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is known for its toxicological, psychopathological and abuse potential. Some environmental conditions, e.g. acoustic stimulation typical of the "rave scene" can influence the toxicity of this drug. We investigated the effects of low doses of MDMA in vivo using Wistar rats in the absence of acoustic stimulation (white noise; 95 Db) demonstrating that ecstasy is able to induce a significant activation (reduction of Electrocortical total power) of the telencephalic cortex that spontaneously reverts in the absence of sensorial stimuli, whereas it persists for several days if, in addition to MDMA, the animals are exposed to acoustic stimulation. Our data demonstrate that low doses of MDMA are able to reduce electrocortical total power, and that this effect is potentiated by sensorial stimuli commonly present in certain environments, such as rave parties.
Content may be subject to copyright.
BioMed Central
Page 1 of 6
(page number not for citation purposes)
BMC Neuroscience
Open Access
Research article
Electrocortical effects of MDMA are potentiated by acoustic
stimulation in rats
Michelangelo Iannone*
1
, Stefania Bulotta
2
, Donatella Paolino
2
,
Maria Cristina Zito
2
, Santo Gratteri
2
, Francesco S Costanzo
†3
and
Domenicantonio Rotiroti
†1,2
Address:
1
CNR – Institute of Neurological Science, Section of Pharmacology, Catanzaro, 88021, Roccelletta di Borgia, Catanzaro, Italy,
2
Faculty of
Pharmacy, University "Magna Græcia" of Catanzaro, Catanzaro, 88021, Roccelletta di Borgia (CZ) Catanzaro, Italy and
3
Faculty of Medicine and
Surgery, University "Magna Græcia" of Catanzaro, Viale Europa, Località Germaneto, Catanzaro, Italy
Email: Michelangelo Iannone* - m.iannone@isn.cnr.it; Stefania Bulotta - bulotta@unicz.it; Donatella Paolino - dpaolino@unict.it;
Maria Cristina Zito - crizito@libero.it; Santo Gratteri - m.iannone@isn.cnr.it; Francesco S Costanzo - fsc@unicz.it;
Domenicantonio Rotiroti - rotiroti@unicz.it
* Corresponding author †Equal contributors
Abstract
Background: 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is known for its
toxicological, psychopathological and abuse potential. Some environmental conditions, e.g. acoustic
stimulation typical of the "rave scene" can influence the toxicity of this drug.
Results: We investigated the effects of low doses of MDMA in vivo using Wistar rats in the
absence of acoustic stimulation (white noise; 95 Db) demonstrating that ecstasy is able to induce a
significant activation (reduction of Electrocortical total power) of the telencephalic cortex that
spontaneously reverts in the absence of sensorial stimuli, whereas it persists for several days if, in
addition to MDMA, the animals are exposed to acoustic stimulation.
Conclusion: Our data demonstrate that low doses of MDMA are able to reduce electrocortical
total power, and that this effect is potentiated by sensorial stimuli commonly present in certain
environments, such as rave parties.
Background
The use of illicit drugs such as 3,4-Methylenedioxymeth-
amphetamine (MDMA; ecstasy) has increased among
young people in Europe and North America [1,2] over the
past years.
Concern has been expressed about the increasing popular-
ity of this stimulant drug and its association with certain
youth subcultures, in particular the dance music scene [3].
The widespread use of ecstasy is due to its ability to pro-
duce feelings of euphoria and energy and a desire to
socialize. In addition to these positive effects, MDMA is
relatively inexpensive to produce and purchase and has
the reputation of being safer than other recreational
drugs.
Yet there is mounting evidence that ecstasy does not
deserve this rosy reputation. In fact, evidence has been
accumulated, both in human and animal studies, that
Published: 16 February 2006
BMC Neuroscience 2006, 7:13 doi:10.1186/1471-2202-7-13
Received: 28 July 2005
Accepted: 16 February 2006
This article is available from: http://www.biomedcentral.com/1471-2202/7/13
© 2006 Iannone et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0
),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BMC Neuroscience 2006, 7:13 http://www.biomedcentral.com/1471-2202/7/13
Page 2 of 6
(page number not for citation purposes)
The effects of MDMA and acoustic stimulation on ECoG power spectrumFigure 1
The effects of MDMA and acoustic stimulation on ECoG power spectrum. Effects of MDMA administration in the
presence or absence of sound stimulation on Electrocortical (ECoG) power spectrum power in rats at various times after
administration. (A) short term (180 min) and (B) long term (5 days) evaluation of ECoG power changes.
A
0
10
20
30
40
50
60
70
80
90
100
110
120
30 60 90 180
Time (minutes) from administration
% changes of ECoG spectrum power (
P
V)
saline
saline + sound
MDMA 3 mg/Kg
MDMA 3 mg/Kg + sound
MDMA 6 mg/Kg
MDMA 6 mg/Kg + sound
*p<0,001 vs. saline, saline+sound, MDMA 3 mg/Kg, MDMA 6 mg/Kg
**p<0.001 vs. saline, saline+sound, MDMA 3 mg/Kg
***p<0.001 vs. saline, saline+sound, MDMA 3 mg/Kg, MDMA 3 mg/Kg+sound, MDMA 6mg/Kg
**
*
*
*
*
***
***
***
***
**
**
**
% changes of ECoG spectrum power ( PV)
*
*
*
130
120
110
100
90
80
70
60
50
40
30
20
10
0
B
24 hours 3 days 5 days
Time from administration
*p<0.001vs. Saline, saline+sound, MDMA 3 mg/Kg, MDMA 3 mg/Kg+sound, MDMA 6 mg/Kg
BMC Neuroscience 2006, 7:13 http://www.biomedcentral.com/1471-2202/7/13
Page 3 of 6
(page number not for citation purposes)
shows the possible risks engendered by the consumption
of MDMA [4]. In many reviews these risks are extensively
discussed in terms of toxicity, psychopathology and abuse
potential associated with acute and chronic use [5].
It is also clear that some environmental conditions can
influence the toxicity of this drug in humans. For example,
one of the consequences of the use of ecstasy at "raves" is
the increase in body temperature that is due to a direct
action of the drug on the thermoregulatory system, to the
intense muscular activity and to elevated environmental
temperatures. In addition, evidence from research done
with an assortement of animal species from rodents to
non-human primates, has shown that ecstasy is neuro-
toxic [5]. In fact, it has been shown that ecstasy is able to
cause serotonergic [6,7] and dopaminergic [8] neuronal
toxicity in every animal species tested and short-term
changes in the noradrenergic system [5].
It has also been repeatedly demonstrated that electroen-
cephalography may be a cheap and effective tool for
examining neurotoxic effects of MDMA in humans where
ecstasy use is positively correlated with absolute power
changes in some frequency bands [4,9].
One of the questions which need addressing by research is
how other factors typical of the "rave scene", such as sen-
sorial auditory (techno music) stimuli, can affect higher
neural functions and in particular electrocortical activity
[10].
Based on these evidences, we investigated whether sound
stimulation affects electrocorticographic changes of total
spectrum power induced by simultaneous administration
of low doses of MDMA in rats.
Results
Short term evaluation
In the short term evaluation set of experiments, the
administration of saline did not induce any modification
in ECoG total spectrum power values in rats exposed to
acoustic stimulation with respect to non-stimulated ani-
mals (Fig 1A).
The systemic administration of MDMA (3 mg/kg) was not
able to modify ECoG total spectrum power values with
respect to saline treated animals. On the contrary, in
MDMA-treated (3 mg/Kg) animals, acoustic stimulation
induced a significant reduction in ECoG total spectrum
power with respect to saline -sound off (P < 0.001; F =
0.92), saline -sound on (P < 0.001; F = 0.94) and MDMA-
sound off (P < 0.001; F = 1.2) treated animals (Fig. 1A).
MDMA administered at the dose of 6 mg/kg -sound off
induced a marked decrease of ECoG total spectrum power
in comparison to control (saline-treated sound off; P <
0.001; F = 0.89) and MDMA (3 mg/Kg) -sound off (P <
0.001; F = 0.78) group. Sensorial stimulation enhanced
ECoG activation with respect to the control (saline-treated
-sound on; P < 0.001; F = 0.96), MDMA (3 mg/Kg) -sound
off/sound on (P < 0.001; F = 0.95/P < 0.001; F = 0.82) and
MDMA 6 mg/Kg -sound off (P < 0.001; F = 0.97) (Fig. 1A).
In all the experiments the effects of MDMA became evi-
dent within 1–3 min after the treatment.
Long term evaluation
In the long term evaluation set of experiments, animals
treated with saline-sound off did not show any change of
ECoG total spectrum power values with respect to rats
treated with saline-sound on, MDMA 3 mg/Kg -sound off,
6 mg/Kg -sound off and MDMA 3 mg/kg -sound on. These
effects lasted 120–180 min after administration and the
evaluation of ECoG total spectrum power 24 h, 3 and 5
days after treatment, did not evidence any difference with
respect to the control (saline-treated) group (Fig. 1B).
On the contrary, the long term evaluation of ECoG
parameters in animals treated with the higher dose of
MDMA (6 mg/kg) -sound on, evidenced a significant
decrease of total spectrum power values 24 h, 3 and 5 days
after treatment with respect to the control (saline-sound
off; P < 0.001; F = 0.90), saline-sound on (P < 0.001; F =
0.88), MDMA (3 mg/Kg) -sound off (P < 0.001; F = 0.87)/
-sound on (P < 0.001; F = 0.95) and to MDMA (6 mg/Kg)
-sound off (P < 0.001; F = 0.94) treated animals.
Discussion
The most relevant finding in these experiments is that rats
exposed to an acoustic stimulation (95 Db) that per se
does not modify the electrocortical parameters evaluated,
show, after the administration of MDMA, a marked
increase in electrocortical activity with respect to animals
treated with the same dose of drug but in absence of sen-
sorial stimulation.
In particular, the lower dose of MDMA used (3 mg/Kg)
was not able to modify electrocortical parameters consid-
ered only in absence of sound stimulation when, in the
same treatment group, the administration of sound signif-
icantly reduced the ECoG power. In addition, the admin-
istration of a single dose of 6 mg/kg of MDMA, induced
(in the presence of acoustic stimulation), significant stim-
ulation of the electrical activity of the brain cortex lasting
for five days after the administration of the drug.
The mechanisms underlying these differences in the dura-
tion of effects of similar treatments (MDMA 3 or 6 mg/kg
-sound on) remain obscure; however, one might speculate
that the higher (6 mg/kg) dosage of MDMA used in the
BMC Neuroscience 2006, 7:13 http://www.biomedcentral.com/1471-2202/7/13
Page 4 of 6
(page number not for citation purposes)
present study might have produced a comparable cross-
sensitisation of the animals to react with higher (and long
lasting) electrocortical activity to acoustic stimuli.
Also the neurochemical basis of the synergism between
noise exposure and MDMA call for more in-depth studies
aimed at disclosing the fine mechanisms underlying this
enhancement. In fact it has been well demonstrated that
exposure to MDMA produces in mice long-lasting EEG
changes and latent brain hyperexcitability, as shown by
persistent changes in baseline and activated EEG, seizure
facilitation and latent metabolic hyperactivity and that
these effects are concomitant with monoamine depletion
within limbic regions and basal ganglia [8], and studies
focused on the basal ganglia circuitry [11], evidentiate
that neurotoxicity affect either serotonin (5-HT) or/and
dopamine (DA) nerve endings.
Indeed, the data available in literature mainly relate to
tests on animals, in which the short- and long-term neu-
rotoxic effects of MDMA are evaluated following adminis-
tration of high doses (ranging from 10 to 20 mg/kg)
which in some studies are repeated for as long as seven
consecutive days [1,5,8,10].
It has been also well demonstrated that acoustic stimula-
tion combined with ecstasy produces a selective enhance-
ment of neurotoxicity (nigrostriatal damage) [8] and
cardiotoxicity [12] in the mouse.
Despite the increasimg number of evidences demonstrat-
ing the synergism between noise and MDMA in inducing
toxical effects, it is very difficult to indicate the mechanism
underliyng these effects. The persistence of the electrocor-
tical effects need in-depht studies aimed at elucidating the
link between serotonergic and acoustic systems and the
biochemical changes induced by MDMA and noise –
treatment.
Our experiments evaluated the effect on animals of low
doses of MDMA associated with sensorial (acoustic stim-
uli) comparable to those occurring in human life within
young people's social gatherings of the "rave" or "techno"
type, whose habitués are known to regularly take this type
of drug, especially during parties chiefly characterised by
strong sensorial stimulations.
Conclusion
Taken together, our data demonstrate that MDMA, even
taken in low doses, is capable of reducing the total power
of the electrocorticographic spectrum, a parameter for the
evaluation of the activation of the telencephalic cortex, in
rats.
In our experimental conditions this activation spontane-
ously reverts in the absence of sensorial stimuli, whereas
it persists for several days if, in addition to MDMA, the
animals are exposed to acoustic stimulation.
We can therefore state that the effects of this drug could be
potentiated by relatively common environmental factors
and stress the potential danger for man of substances that
have been so "popularly" accepted as relatively "safe"
owing to their "short term" effects.
Methods
Adult male Wistar rats weighing 250–280 g (three months
old) were obtained from Charles River (Milan, Italy) and
housed in a temperature (20°C) and humidity (60%)-
controlled colony room. The colony, in pathogen-free
conditions, was maintained in a 12 h light/dark cycle with
light on at 7.00 a.m. with both laboratory food and tap
water available ad libitum.
The experimental protocol and procedures used meet the
guidelines of the Ministry of Health (G.U. n. 40, Feb. 18,
1992) for the use of laboratory animals in Italy.
Rats were anesthetized with chloral-hydrate (400 mg/kg
i.p., Sigma Chemical Co., St. Louis, MO, USA) and placed
in a Kopf stereotaxic apparatus. For each rat, four hand-
made steel epidural electrodes were inserted through a
hole drilled in the skull onto each fronto-parietal cortex 2
mm behind the bregma and ± 2 mm laterally to the mid-
line. In detail, they were produced from a 1.5-mm diame-
ter wire, which was molded and flattened on one side, and
was then bent to 90°. The flattened end of the electrode
possessed a recording surface of 2.25 mm
2
and was placed
right below the skull through a burr hole. The electrodes
were kept in place by dental acrylic cement and jeweler
screws, for chronic EEG recordings (see [11]). The animals
were allowed 1 week to recover before testing.
Before experiments, the animals were placed individually
in a sound-proof Mercury chamber modified to allow
simultaneous ECoG recording (Scalone, Italy) and
allowed 30 min to acclimatize to the new environment.
In awake, freely moving animals, ECoG traces were con-
tinuously recorded for 60 min before and 180 min after
drug injection by connecting the electrodes to an 8 chan-
nel EEG recorder (ERA-9; OTE Biomedica, Florence, Italy).
For long-term evaluation, animals were returned to testing
in the same conditions 24 h, 3 and 5 days after treatment.
Spontaneous and treatment-induced changes in the
domain of the total ECoG spectrum power (0.25–16 Hz)
were monitored continuously for periods of 30 seconds.
Computerized quantitization of changes in ECoG signal
amplitude (µV) was obtained with the aid of a Berg-Fou-
BMC Neuroscience 2006, 7:13 http://www.biomedcentral.com/1471-2202/7/13
Page 5 of 6
(page number not for citation purposes)
rier analyser (OTE Biomedica, Florence, Italy). For statisti-
cal purposes, ECoG signal amplitude was expressed as
mean ± s.e. mean percentage changes from control ampli-
tude. The resulting means from control and test experi-
ments were evaluated statistically for differences by prior
two way ANOVA followed by Tukey Test. The parameters
evaluated were: stimulation (sound on vs sound off) and
treatment (saline vs dose of MDMA used). ECoG activity
Electrocorticographic activity changes in dependence of sensorial stimuli in MDMA – treated ratsFigure 2
Electrocorticographic activity changes in dependence of sensorial stimuli in MDMA – treated rats. Sequential
spectral analysis illustrating the effects of (A) MDMA (6 mg/kg; i.p.) and (B) sound (95 dB) + MDMA (6 mg/Kg; i.p.) on electro-
corticographic activity in rats. The ECoG activity, evaluated at various times after treatment shows a marked decrease in total
power after simultaneous administration of sound (A VS B).
A-sound off B-sound on
180
120
90
60
30
0
04 812160481216
= MDMA administration
= Sound on
Time
(
minutes
)
Frequency bands (Hz)
Publish with Bio Med Central and every
scientist can read your work free of charge
"BioMed Central will be the most significant development for
disseminating the results of biomedical research in our lifetime."
Sir Paul Nurse, Cancer Research UK
Your research papers will be:
available free of charge to the entire biomedical community
peer reviewed and published immediately upon acceptance
cited in PubMed and archived on PubMed Central
yours — you keep the copyright
Submit your manuscript here:
http://www.biomedcentral.com/info/publishing_adv.asp
BioMedcentral
BMC Neuroscience 2006, 7:13 http://www.biomedcentral.com/1471-2202/7/13
Page 6 of 6
(page number not for citation purposes)
was monitorized 24 h, 3 and 5 days after by repeating
recording in the same conditions but omitting pharmaco-
logical treatment or acoustic stimulation.
For the sensorial stimulation rats were exposed for all the
duration of the first electrocortical recording (60 min
before and 180 min after administration; in no case ani-
mals were exposed to another session of acoustic stimula-
tion) to continuous white noise produced by two
loudspeakers (set at 95 dB) driven by a white-noise gener-
ator (0–26 kHz), which was installed 30 cm apart from
the cage. The sound level was monitored by a sound level
meter (Quest electronics, 215) and it was uniform
throughout tha cage. The level of loud noise was selected
in order to mimic the same intensity to which humans are
exposed in the discoteques (95 dB is the maximum inten-
sity permitted from the Italian law).
3,4-Methylenedioxymethamphetamine, purchased from
SALARS (Como, Italy), was dissolved in normal saline.
Rats (n = 5 for each group) were randomly assigned to one
of the regimens, each receiving one intraperitoneal injec-
tion of either normal saline (0.5 ml) or MDMA (3 or 6
mg/kg; 0.5 ml) with sound (95 Db) on or off.
Thus, the treatment regimens were as follows: Sound off +
saline; Sound on + saline; Sound off + MDMA; Sound on
+ MDMA. The administration of sound was started 60
min before the injection of saline or MDMA.
Authors' contributions
MI coinceived and coordinated the study and performed
electrocortical analisys. SB, DP and MCZ carried the study
and performed the statistical analysis. SG participated in
design and coordination of the study and helped to draft
the manuscript. FSC and DR supervised the study. All
authors read and approved the final manuscript.
Acknowledgements
Our thanks go to Mr Frustaci S., Mr Macrì A. and Mr Saturnino D. for excel-
lent technical assistance, to Mr Apuzzo D. for administrative assistance and
for english revision of the manuscript to Mrs Lynn Ann Whitted. To mr.
Benito Rocco Scalone (Girifalco, Catanzaro, Italy) go our particular thanks
for the realization of the technical apparatus. This work was economically
supported from the Presidence of Calabria Region, Italy.
References
1. Baumgarten HG, Lachenmayer L: Serotonin neurotoxins – past
and present. Neurotox Res 2004, 6:589-614.
2. Peroutka SJ: Incidence of recreational use of 3,4-methylened-
imethoxymethamphetamine (MDMA, "ecstasy") on an
undergraduate campus. N Engl J Med 1987, 317:1542-1543.
3. Randall T: 'Rave' scene, ecstasy use, leap atlantic. JAMA 1992,
268:1506.
4. Gamma A, Frei E, Lehmann D, Pascual-Marqui RD, Hell D, Vollenwei-
der F: Mood state and brain electric activity in Ecstasy users.
Neuroreport 2000, 11:157-162.
5. Kalant H: The pharmacology and toxicology of "ecstasy"
(MDMA) and related drugs. CMAJ 2001, 165:917-928.
6. O'Hearn E, Battaglia G, De Souza EB, Kuhar MJ, Molliver ME: Meth-
ylendioxyamphetamine (MDA) and methylendioxymetham-
phetamine (MDMA) cause selective ablation of
serotoninergic axon terminal in forebrain: immunocyto-
chemical evidence for neurotoxicity. J Neurosci 1988,
8:2788-2803.
7. Ricaurte GA, Yuan J, McCann UD: 3,4-Methylene-dioxymetham-
phetamine ('ecstasy') – induced serotonin neurotoxicity:
studies in animals. Neuropsycobiology 2000, 42:5-10.
8. Gesi M, Ferrucci M, Giusiani M, Lenzi P, Lazzeri G, Alessandri MG, Sal-
vadorini A, Fulceri F, Pellegrini A, Fornai F, Paparelli A: Loud noise
enhances nigrostriatal dopamine toxicity induced by MDMA
in mice. Microsc Res Tech 2004, 64:297-303.
9. Dafters RI, Duffy F, O'Donnell PJ, Bouquet C: Level of use of 3,4-
methylenedioxymethamphetamine (MDMA or Ecstasy) in
humans correlates with EEG power and coherence. Psychop-
harmacology 1999, 145:82-89.
10. Morton A, Jennifer CA, Hickey MA, Dean LC: Methamphetamine
toxicity in mice is potentiated by exposure to loud music.
Neuroreport 2001, 12:3277-3281.
11. Giorgi FS, Pizzanelli C, Ferrucci M, Lazzeri G, Faetti M, Giusiani M,
Pontarelli F, Busceti L, Murrib L, Fornaia F: Previous exposure to
3,4-methylenedioxymethamphetamine produces long-last-
ing alteration in limbic brain excitability measured by elec-
troencephalogram spectrum analysis, brain metabolism and
seizure susceptibility. Neuroscience 2005, 136:43-53.
12. Gesi M, Soldani P, Lenzi P, Ferrucci M, Giusiani A, Fornai F, Paparelli
A: Ecstasy during loud noise exposure induces dramatic
ultrastructural changes in the heart. Pharmacol Toxicol 2002,
91:29-33.
... However, gathering evidence is beginning to show the neurotoxic effects of amphetamines and amphetamine derivatives may be increased by loud noise (Gesi et al., 2004;Scholey et al., 2004). Iannone et al. reported a marked increase in electrocortical activity of the telencephalic cortex in rats treated with MDMA (3 mg/kg and 6 mg/kg) and acoustic stimulation (white noise; 95 Db) compared to rats that received MDMA in the absence of additional environmental sound (Iannone et al., 2006). In another study, mice given methamphetamine (75 mg/kg) while exposed to loud music (95 Db) showed a change in a number of behavioral parameters and experienced more seizures than mice given the same dose of methamphetamine in silence (ambient noise, 55 Db) or in the presence white noise (95 Db) (Morton et al., 2001). ...
... For example, significant changes in electrocortical activity were observed in rats receiving MDMA with additional acoustic stimulation compared to animals that received the same dose of MDMA without additional noise. In addition, no change in electrocortical activity was observed in animals exposed to loud white noise (95 dB) as compared to control animals that received no additional sound (Iannone et al., 2006). Other work has shown a relationship between noise alone and monoamine metabolite (DOPAC, HVA, and 5-HIAA) levels in the striatum of mice (Tsai et al., 2005), though the intensity of white noise (110 dB) was much higher than that of the present study (70 dB). ...
Article
Full-text available
The amphetamine derivative, 3,4-methylenedioxymethamphetamine (MDMA), is a popular drug often taken by young adults at dance clubs or rave parties. Laser light shows, fast-paced electronic music, and hot crowded dance floors are characteristic of these events, and Ecstasy users report that the acute effects of the drug are potentiated by these stimulatory conditions. However, it remains largely unknown how environmental stimuli impact the neurochemical and physiological effects of MDMA. The aim of the first study presented in this dissertation was to investigate how auditory stimuli (music, white noise, and no additional sound) influence MDMA conditioned place preference (CPP), self-administration, and nucleus accumbens (NAcc) dopamine (DA) and serotonin (5-HT) responses. Findings revealed a significant CPP for animals exposed to white noise during MDMA conditioning trials. After self-administration of MDMA (1.5 mg/kg), NAcc DA and 5-HT were highest in rats exposed to music during the test session. The second study aimed to investigate the effects of ambient temperature (23°or 32°C) on long-term MDMA self-administration and neurochemical responses. Results indicated no difference in self-administration or locomotor activity rates for the high versus room temperature groups across sessions. However, MDMA (3.0 mg/kg) administered in high ambient temperature resulted in significantly greater NAcc serotonin release compared to when taken at room temperature, but no differences in dopamine response was determined between the two conditions. Overall, these results indicate that auditory and thermal stimuli can effect MDMA-induced behavioral and neurochemical responses. The last aim tested a novel apparatus and method for use in animal models of drug reinforcement. By combining traditional CPP and self-administration procedures, this approach provided more informative data and circumvented some inherent drawbacks of each method alone. In addition to confirming the ability to produce drug conditioned place preferences after short- and long-term experiments, the long-term version of the procedure revealed a significant positive relationship between lever response rate and CPP magnitude. Therefore, this experimental design can be used to identify subgroups of rats that may vary in sensitivity to drug motivational effects. Further study of these populations may be useful in the development of behavioral and pharmacological therapies for drug addiction. Pharmacy
... I felt as though I completely understood what raves are all about -including the music, which had always grated on me" Some scientists have tried to test whether the pharmacological or toxicological effects of MDMA are potentiated by loud acoustical stimuli. In one experiment, cortical activity was found to be activated for as long as five days after rats were exposed to 95dB sound combined with a low dose of MDMA whereas if the drug was given in a quiet environment, the effects of the drug were transient and lasted less than one day (Iannone et al. 2006). Another group also found that MDMA caused more damage to dopaminergic nerves in the brain if the animals were subjected to 6 hours of noise (100 dB) exposure. ...
Book
Rhythm lies at the core of popular music. In fact, the rhythmic component of music may be one reason why all human societies have enjoyed and used music. Today, artists producing popular music wish to entertain their listeners – for the audience, hearing these songs is a hedonistic experience. Similarly, the background to consumption of illicit drugs is hedonism. There are differences in the ways that the illicit drugs affect brain neurochemistry in other regions of the brain, affecting other neurotransmitters. In this book, we consider if and how six illicit drugs (cannabis; amphetamines; heroin; MDMA [ecstasy]; cocaine; LSD) have influenced popular music – and how this influence can be traced to the changes they evoke in brain neurochemistry. Amphetamines speed up the brain’s sense of time, cannabis not only slows down the brain’s sense of time passing, it also disturbs the seamless processing of information. MDMA is an amphetamine but its effects extend to other transmitters, so while electronic dance music is fast, it is not associated with violence. Heroin is undoubtedly the most dangerous and we found that heroin-inspired music was egoistic. The music associated with cocaine (1970s disco) was bland, but the crack cocaine, in contrast, is linked with the violence and misogyny of gangsta’ rap. The hallucinogens like LSD tend to evoke synaesthesia and during an LSD trip, the user completely loses the ability to keep track of time. In conclusion, while it is clear that much of the popular music created would probably have been created with or without these drugs, we would argue that nonetheless, the effects evoked by these drugs in the brain, especially in the way that the brain senses the passage of time, are buried in the melodies, rhythms and lyrics of many songs.
... animal and human data has been reconciled by animal tests carried out under distinct environments to mimic such rave scenarios (Turner and Parrott, 2000;Parrott, 2012b). Several environmental factors have been investigated, including warm ambient temperatures, physical activity, loud music, lights, and crowded situations (Malberg and Seiden, 1998;Fantegrossi et al., 2003;Iannone et al., 2006;Stanley et al., 2007;Von Huben et al., 2007;Gilpin et al., 2011). Despite many efforts, the environment explored in laboratory tests appears to have very moderate effects on MDMA toxicity (Green et al., 2004b;Shortall et al., 2013) unless a huge dose (e.g., 20-40 mg/kg) was used for animals (Gordon et al., 1991;Malberg and Seiden, 1998). ...
Article
Full-text available
Rationale: Illicit use of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) may cause a mild or severe form of the serotonin syndrome. The syndrome intensity is not just influenced by drug doses but also by environmental factors. Objectives: Warm environmental temperatures and physical activity are features of raves. The purpose of this study was to assess how these two factors can potentially intensify the syndrome. Methods: Rats were administered MDMA at doses of 0.3, 1, or 3 mg/kg and examined in the absence or presence of warm temperature and physical activity. The syndrome intensity was estimated by visual scoring for behavioral syndrome and also instrumentally measuring changes in symptoms of the syndrome. Results: Our results showed that MDMA at 3 mg/kg, but not 0.3 or 1 mg/kg, caused a mild serotonin syndrome in rats. Each environmental factor alone moderately intensified the syndrome. When the two factors were combined, the intensification became more severe than each factor alone highlighting a synergistic effect. This intensification was blocked by the 5-HT2A receptor antagonist M100907, competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist CGS19755, autonomic ganglionic blocker hexamethonium, and the benzodiazepine-GABAA receptor agonist midazolam but not by the 5-HT1A receptor antagonist WAY100635 or nicotinic receptor antagonist methyllycaconitine. Conclusions: Our data suggest that, in the absence of environmental factors, the MDMA-induced syndrome is mainly mediated through the serotonergic transmission (5-hydroxytryptamine (5HT)-dependent mechanism) and therefore is relatively mild. Warm temperature and physical activity facilitate serotonergic and other neural systems such as glutamatergic and autonomic transmissions, resulting in intensification of the syndrome (non-5HT mechanisms).
... Globus et al. (1978) andIannone et al. (2006) have shown that loudness scaling is state dependent and can be pharmacologically altered. ...
... For example, significant changes in electrocortical activity were observed in rats receiving MDMA with additional acoustic stimulation compared to animals that received the same dose of MDMA without additional noise. In addition, no change in electrocortical activity was observed in animals exposed to loud white noise (95 dB) as compared to control animals that received no additional sound [12]. Other work has shown a relationship between noise alone and monoamine metabolite (DOPAC, HVA, and 5-HIAA) levels in the striatum of mice [29], though the intensity of white noise (110 dB) was much higher than that of the present study (70 dB). ...
Article
Full-text available
MDMA (3,4-methylenedioxymethamphetamine), also known as ecstasy, is a popular drug often taken in environments rich in audio and visual stimulation, such as clubs and dance parties. The present experiments were conducted to test the notion that auditory stimulation influences the rewarding effects of MDMA. In Experiment 1, a conditioned place preference (CPP) procedure was conducted in which rats received MDMA (1.5mg/kg, s.c.) in a distinctive environment accompanied by music (65-75dB), white noise (70dB), or no added sound. Animals were pretreated with saline on alternating days in an alternate environment. Results revealed CPP in animals exposed to white noise during MDMA trials. For Experiment 2, rats from Experiment 1 had access to operant levers that delivered intravenous MDMA (0.5mg/kg/inj) or saline (0.1ml) on alternate days in the presence or absence of the same types of auditory stimuli as previously experienced. After three each of MDMA and non-reinforced (saline) sessions, animals were tested for NAcc DA and 5-HT responses to MDMA (1.5mg/kg) or saline under the same stimulus conditions. Findings revealed that NAcc DA and 5-HT increased after an MDMA injection, and both DA and 5-HT were significantly highest in animals exposed to music during the test session. These results indicate that paired sensorial stimuli can engage the same systems activated during drug use and enhance neurochemical and behavioral responses to MDMA administration.
Article
To a generation of party-goers, Ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] represents one of the safest illegal drugs available and, superficially, evidence supports this notion. Compared with other recreational drugs, there have been relatively few Ecstasy-related deaths and there is little direct evidence for short-term neurotoxicity at recreational doses. However, Ecstasy causes 5-hydroxytryptamine (5-HT) nerve-terminal damage in rats, mice and monkeys, and, in several studies, the damage is irreversible.
Article
Many of the effects of very loud music are now known, but not the long-term cognitive effects. This is an important question, since loud music is now ubiquitous. Investigation is called for, including the collation of research that is currently hard to find. Two hundred teenagers aged 12-19 completed a questionnaire on 'Very Loud Music' and their responses are discussed.
Article
Since its emergence as a recreational club drug in the 1970s, 3-4 methylenedioxy-methamphetamine's usage, more commonly known as ecstasy or MDMA, has risen rapidly through the 1990s, mainly among the teens and young adults of the United States and Europe due to its various perceived social effects. As a result of this sudden rise and the unknown nature of the drug's short- and long-term effects on brain chemistry and function, an ever increasing attention in the political, medical, and scientific fields has occurred which lead to increased mainstream media coverage. Although MDMA is not a performance-enhancing drug in the current use, its abuse is highly associated with motives of euphoria, increased sociability and enhanced energy that can lead to altered cognitive performance. Thus, due to the short-term, acute stimulant effects of MDMA, it is currently viewed by abusers as a performance-enhancing drug affecting both the mood and physical abilities. Given the heightened interest in MDMA as a party drug and in order to shed light on what is currently known about it that leads to its perceived perception as performance enhancing drug, this article will provide a comprehensive overview on MDMA's role as a social facilitator along with its usage history, epidemiology, and its adverse neurotoxic effects.
Chapter
Full-text available
Music and consciousness are things we do. . . . Achieving consciousness, from the Latin con (with) and scire (to know), is the central activity of human knowledge. At the heart of the word is a concept of mutuality, knowing with others. Our consciousness is a mutual activity; it is performed. (Aldridge, 2006, p. 10)
Article
Full-text available
The psychotropic amphetamine derivatives 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) have been used for recreational and therapeutic purposes in man. In rats, these drugs cause large reductions in brain levels of serotonin (5-HT). This study employs immunocytochemistry to characterize the neurotoxic effects of these compounds upon monoaminergic neurons in the rat brain. Two weeks after systemic administration of MDA or MDMA (20 mg/kg, s.c., twice daily for 4 d), there is profound loss of serotonergic (5-HT) axons throughout the forebrain; catecholamine axons are completely spared. Regional differences in drug toxicity are exemplified by partial sparing of 5-HT axons in hippocampus, lateral hypothalamus, basal forebrain, and in some areas of neocortex. The terminals of 5-HT axons are selectively ablated, while axons of passage and raphe cell bodies are spared. Thickened preterminal fibers exhibit increased staining due to damming-up of neurotransmitter and other axonal constituents. Fine 5-HT axon terminals are extremely vulnerable to these drugs, whereas terminal-like axons with large varicosities survive, raising the possibility that some 5-HT axons may be resistant to the neurotoxic effects. At short survivals, visualization of greatly swollen, fragmented 5-HT axons provides anatomic evidence for degeneration of 5-HT projections. The results establish that MDA and MDMA produce structural damage to 5-HT axon terminals followed by lasting denervation of the forebrain. Both drugs have similar effects, but MDA produces a greater reduction of 5-HT axons than does MDMA at the same dosage. The selective degeneration of 5-HT axons indicates that these drugs may serve as experimental tools to analyze the organization and function of 5-HT projections. Caution should be exercised until further studies determine whether these compounds may be hazardous in man.
Article
Full-text available
Despite animal studies implicating 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) in serotonergic neurotoxicity, there is little direct evidence of changes in neural function in humans who use MDMA as a recreational drug. The present study investigated whether there is a correlation between quantitative EEG variables (spectral power and coherence) and cognitive/mood variables, and level of prior use of MDMA. Twenty-three recreational MDMA users were studied. Resting EEG was recorded with eyes closed, using a 128-electrode geodesic net system, from which spectral power, peak frequency and coherence levels were calculated. Tests of intelligence (NART), immediate and delayed memory, frontal function (card sort task), and mood (BDI and PANAS scales) were also administered. Pearson correlation analyses were used to examine the relationship between these measures and the subject's consumption of MDMA during the previous 12-month period. Partial correlation was used to control for the use of other recreational drugs. MDMA use was positively correlated with absolute power in the alpha (8-12 Hz) and beta (12-20 Hz) frequency bands, but not with the delta (1-3 Hz) or theta (4-7 Hz) bands. MDMA use was negatively correlated with EEG coherence, a measure of synchrony between paired cortical locations, in posterior brain sites thought to overly the main visual association pathways of the occipito-parietal region. MDMA use did not correlate significantly with any of the mood/cognitive measures except the card sort task, with which it was weakly negatively correlated. Alpha power has been shown to be inversely related to mental function and has been used as an indirect measure of brain activation in both normal and abnormal states. Reduced coherence levels have been associated with dysfunctional connectivity in the brain in disorders such as dementia, white-matter disease and normal aging. Our results may indicate altered brain function correlated with prior MDMA use, and show that electroencephalography may be a cheap and effective tool for examining neurotoxic effects of MDMA and other drugs.
Article
Full-text available
Resting EEG during open and closed eyes and subsequent mood ratings were obtained from 15 Ecstasy users and 14 Ecstasy-naive controls. Absolute spectral power on the scalp, and the three-dimensional, intracerebral distribution of neuroelectric activity using low resolution brain electromagnetic tomography (LORETA) were computed. LORETA revealed global increases of theta, alpha 1 and beta 2/3 power during eyes open in Ecstasy users, and spectral analyses revealed a right-posterior increase of alpha 2 power (confirmed by LORETA) and increased beta band activity during open eyes. Ecstasy users had higher levels of state depressiveness, emotional excitability and a trend-level increase in state anxiety. The observed differences may be related to regular exposure to Ecstasy or other illicit drugs, or may be pre-existing.
Article
"ECSTASY" (MDMA) AND RELATED DRUGS ARE AMPHETAMINE DERIVATIVES that also have some of the pharmacological properties of mescaline. They have become popular with participants in "raves," because they enhance energy, endurance, sociability and sexual arousal. This vogue among teenagers and young adults, together with the widespread belief that "ecstasy" is a safe drug, has led to a thriving illicit traffic in it. But these drugs also have serious toxic effects, both acute and chronic, that resemble those previously seen with other amphetamines and are caused by an excess of the same sympathomimetic actions for which the drugs are valued by the users. Neurotoxicity to the serotonergic system in the brain can also cause permanent physical and psychiatric problems. A detailed review of the literature has revealed over 87 "ecstasy"-related fatalities, caused by hyperpyrexia, rhabdomyolysis, intravascular coagulopathy, hepatic necrosis, cardiac arrhythmias, cerebrovascular accidents, and drug-related accidents or suicide. The toxic or even fatal dose range overlaps the range of recreational dosage. The available evidence does not yet permit an accurate assessment of the size of the problem presented by the use of these drugs.
Article
THE BRITISH rave counterculture, and its liberal use of ecstasy (MDMA), has become a hot export to the United States, wrapped in a high-tech music and video package and supported by low-tech laboratories that illicitly produce the drug stateside. An August 19,1992, article by United Press International says that a clampdown on rave parties by British authorities has inspired several English rave promoters to move their business to the United States. Staged in empty warehouses or open fields outside San Francisco or Los Angeles, their parties are drawing thousands of young Californians on designated weekend nights. Partygoers—attired in Cat in the Hat-hats and psychedelic jumpsuits—pay $20 at the door to dance all night to heavily mixed, electronically generated sound, surrounded by computer-generated video and laser light shows. They pay another $3 to $5 for "smart drinks"— amino acid—laced beverages that reputedly enhance energy and alertness. And for another $20
Article
The popular recreational drug, (+/-)3, 4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') is a potent and selective brain serotonin (5-HT) neurotoxin in animals. MDMA-induced 5-HT neurotoxicity can be demonstrated using a variety of neurochemical, neuroanatomical and, more recently, functional measures of 5-HT neurons. Although the neurotoxic effects of MDMA in animals are widely accepted, the relevance of the animal data to human MDMA users has been questioned, largely because dosages of drugs used in animals are perceived as being much higher than those used by humans. In the present paper, we review the extensive body of data demonstrating that MDMA produced toxic effects on brain 5-HT neurons in animals and present new data indicating that levels of the type 2 vesicular monoamine transporter are reduced in MDMA-treated animals, providing further indication of MDMA's 5-HT neurotoxic potential. Further, we demonstrate, using principles of interspecies scaling, that dosages of MDMA known to be neurotoxic in animals fall squarely in the range of dosages used typically by recreational MDMA users.
Article
"Ecstasy" (MDMA) and related drugs are amphetamine derivatives that also have some of the pharmacological properties of mescaline. They have become popular with participants in "raves," because they enhance energy, endurance, sociability and sexual arousal. This vogue among teenagers and young adults, together with the widespread belief that "ecstasy" is a safe drug, has led to a thriving illicit traffic in it. But these drugs also have serious toxic effects, both acute and chronic, that resemble those previously seen with other amphetamines and are caused by an excess of the same sympathomimetic actions for which the drugs are valued by the users. Neurotoxicity to the serotonergic system in the brain can also cause permanent physical and psychiatric problems. A detailed review of the literature has revealed over 87 "ecstasy"-related fatalities, caused by hyperpyrexia, rhabdomyolysis, intravascular coagulopathy, hepatic necrosis, cardiac arrhythmias, cerebrovascular accidents, and drug-related accidents or suicide. The toxic or even fatal dose range overlaps the range of recreational dosage. The available evidence does not yet permit an accurate assessment of the size of the problem presented by the use of these drugs.
Article
Methamphetamine (METH) is a drug of abuse used for its stimulant effects. Its neurotoxicity is very variable, and is increased by a number of factors, including crowded conditions and increased ambient temperature. The effects of such factors are increasingly important, with the widespread use of these stimulants at nightclubs and 'raves'. Here, we compared the effect of another dominant feature of nightclubs, continuous loud noise, on the toxicity of METH in mice. We found that mice exposed to loud music exhibited longer lasting stereotypy, an altered place preference in the open field and had more seizures than mice given METH in a quiet setting or when exposed to loud white noise. A greater increase in reactive gliosis was also seen after exposure to METH and loud music. Thus, METH appears to be more toxic when taken while exposed to loud music.