Nootropic and Anti-anxiety Effects of Olive Oil: Relationship with Dopamine and Serotonin Metabolism

Abstract

In recent years, interest in the use of nutraceuticals has risen substantially. Olive oil has been shown to produce a number of therapeutically important effects due to its antioxidant property. The present study concerns neurochemical and behavioral effects of long term administration of low and high doses (0.1 mL/kg and 0.25 mL/kg) of olive oil and associated antioxidant effects in rats. Long term administration of low dose of olive oil increased motor activity in an open field, decreased anxiety in elevated plus maze test, and enhanced memory in Morris water maze test. Whole brain levels of serotonin increased with low dose of olive oil while homovanillic acid (HVA), a metabolite of dopamine increased with both doses of olive oil. Low dose of olive oil increased glutathione peroxidase activity whereas high dose of olive oil decreased malondialdehyde levels in plasma. The results show that particularly low doses of olive oil reduce anxiety and improve learning and memory together with antioxidant properties, brain dopamine and serotonin also play important role in the therapeutically important effects of olive oil.

Full text

Nootropic and An-anxiety Eects of Olive Oil: Relaonship with Dopamine
and Serotonin Metabolism
Atif Raza Cheema M1,2*, Khalid Mahmood2, Darakhshan J Haleem2 and Rafeeq A Khan1
1Faculty of Pharmacy and Pharmaceucal Sciences, Department of Pharmacology, University of Karachi, Karachi, Pakistan
2Neuroscience Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, Internaonal Center for Chemical and
Biological Sciences, University of Karachi, Karachi, Pakistan
*Corresponding author: Af Raza Cheema M, Neuroscience Research Laboratory (P-102), Dr. Panjwani Center for Molecular Medicine and Drug
Research (PCMD), Internaonal Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi-75270, Pakistan, Tel:
922199261300-07; E-mail: afpharmacist3@iccs.edu
Received: January 24, 2018; Accepted: April 18, 2018; Published: April 26, 2018
Citaon: Cheema MAR, Mahmood K, Haleem DJ, Khan RA (2018) Nootropic and An-anxiety Eects of Olive Oil: Relaonship with Dopamine
and Serotonin Metabolism. J Nutraceucals Food Sci Vol.3:No.1:4.
Abstract
In recent years, interest in the use of nutraceucals has
risen substanally. Olive oil has been shown to produce a
number of therapeucally important eects due to its
anoxidant property. The present study concerns
neurochemical and behavioral eects of long term
administraon of low and high doses (0.1 mL/kg and 0.25
mL/kg) of olive oil and associated anoxidant eects in
rats. Long term administraon of low dose of olive oil
increased motor acvity in an open eld, decreased
anxiety in elevated plus maze test, and enhanced memory
in Morris water maze test. Whole brain levels of serotonin
increased with low dose of olive oil while homovanillic
acid (HVA), a metabolite of dopamine increased with both
doses of olive oil. Low dose of olive oil increased
glutathione peroxidase acvity whereas high dose of olive
oil decreased malondialdehyde levels in plasma. The
results show that parcularly low doses of olive oil reduce
anxiety and improve learning and memory together with
anoxidant properes, brain dopamine and serotonin
also play important role in the therapeucally important
eects of olive oil.
Keywords: Olive oil; Anxiety; Memory; Dopamine;
Serotonin
Introducon
In recent years, interest in the use of nutraceucals has
risen substanally, largely because of their ecacy, fewer side
eects, and cost eciency. There is growing need of nootropic
agents because the currently available cognive-enhancing
drugs (psychosmulants) have unwanted side eects such as
psychoc symptoms and abuse potenal [1]. Remission rate
and treatments for psychiatric illnesses such as depression and
anxiety are also not sasfactory [2].
The fruit of Olea europaea L. (Family: Oleaceae) is
commonly known as olive. It is a major component of the
Mediterranean diet. In the last few decades, global
consumpon of olive oil has increased due to increased
awareness of its health benets [3,4]. Olive oil has been used
in tradional medicine due to its anhypertensive and cardio-
protecve eects. It also has an-inammatory, analgesic, and
ancancer eects [5]. However, eects of this oil on
monoamine metabolism have not been widely invesgated
[6].
Despite a number of benecial eects only few studies have
been performed on the eects of olive oil on anxiety and
cognion [6,7]. It has also been reported that 4 weeks
administraon of olive oil at dose of 0.25 mL/kg produces
andepressant and ananxiety eects and this was associated
with a decrease in brain serotonin [5-hydroxytryptamine (5-
HT)] and dopamine (DA) metabolism [6]. In the present study,
potenal ananxiety eects of low and high doses of olive oil
were determined aer one and ve weeks of administraon.
The an-anxiety eect was produced aer 5 weeks but not
one week of oil administraon. Animals were later tested on
water maze for learning acquision and memory retenon.
The animals were killed to collect brain and plasma samples
for determining 5-HT and DA metabolism in the whole brain
and malondialdehyde (MDA) and glutathione peroxidase (GSH-
PX) acvity in the plasma. Food intake and change in body
weight during 5 weeks treatment were also monitored.
Materials and Methods
Experimental animals
Locally bred male albino Wistar rats, weighing 180-230 g
(age approximately 7 weeks) were obtained from Animal
Resource Facility of Dr. Panjwani Center for Molecular
Medicine and Drug Research. They were individually housed in
opaque cages (to avoid eect of social interacon) at
controlled room temperature (22 ± 2°C) and humidity (55 ±
10%) under 12-h light/dark cycle (lights on at 7:00 h). They
were provided standard rodent diet [8] and water ad libitum
Research Article
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during the enre study period. This study was approved by
Instuonal Animal Care and Use Commiee, Internaonal
Center for Chemical and Biological Sciences (ICCBS), University
of Karachi (Protocol#: 2014-0016). Animal study protocol was
conducted in accordance with Naonal Instutes of Health
Guide for Care and Use of Laboratory Animals (NIH Publicaon
No. 85-23, revised 1985).
Oil, chemicals and reagents
Olive oil (100% pure) was purchased from a retail store of
Karachi (imported from Sasso® Via 31 Tavarnelle Val di Pesa,
Firenze, Italy).
2-Thiobarbituric acid, 5,5-dithiobis (2-nitrobenzoic acid)
(DTNB) or Ellman’s reagent, disodium hydrogen phosphate
anhydrous (di-basic) (Na2HPO4), Ethylene-diaminetetra-acec
acid disodium salt 2-hydrate (EDTA-Na2), glutathione (GSH),
hydrogen peroxide soluon 35% by weight (H2O2), sodium
azide, sodium carbonate, sodium dihydrogen phosphate
dihydrate (monobasic) (NaH2PO4.2H2O), and trichloroacec
acid (TCA), DA, homovanillic acid (HVA), dihydroxyphenyl
acec acid (DOPAC), 5-HT creanine sulfate, 5-hydroxyindole
acec acid (5-HIAA), and sodium octyl sulfate (SOS) were
procured from Sigma (St. Louis, MO, USA). HPLC grade
chemicals and reagents were used in HPLC-ECD (High
Performance Liquid Chromatography with Electrochemical
Detector), whereas all other chemicals and reagents were of
analycal grade.
Experimental protocol
Twenty-one rats were divided in to three groups (n=7). All
treatments were orally administered at 09:30 to 10:00 h daily
for ve weeks. Group 1 (control) received tap water. Groups 2
(olive oil 10) and 3 (olive oil 25) were treated with 0.1 mL/kg
and 0.25 mL/kg of olive oil, respecvely. Animals were
acclimazed for one week before the start of experiment.
Cumulave food intake and change in body weight gain were
monitored during the ve weeks treatment. Acvity in a home
cage and open eld was monitored aer ve weeks of drug
treatment from 10:30 to 11:00 h and 11:30 to 12:00 h,
respecvely.
Performance in elevated plus maze test was monitored aer
one and ve weeks of drugs treatment from 12:30 to 13:00 h.
Learning acquision and memory retenon were monitored
on day 34 and 35, respecvely using Morris water maze test.
Aerwards animals were decapitated at 11:30 am to 12:30 pm
to collect whole brain and blood samples. Blood samples were
collected in falcon tubes containing pre-added ancoagulant
(15 mM EDTA per mL blood in a 10:1 rao) and kept at room
temperature for 30 min.
Aer centrifugaon at 4,000 rpm for 12 min the plasma was
separated [9]. Brain and plasma samples were kept at -80°C for
neurochemical analysis by HPLC-ECD and analysis of
anoxidant enzymes using microplate absorbance reader,
respecvely.
Food intake and body weights
Cumulave food intake (g) was determined weekly between
08:30 and 09:30 h by taking the dierence of food given on
week 1 and food le on the following week. Percentage
change in body weight was calculated weekly as: (current body
weight/ preceding week body weight) × 100 [10].
Behavioral studies
Home cage acvity test: Specially designed transparent
Perspex cages (26 × 26 × 26 cm) with sawdust-covered oor
were used to monitor acvity in the familiar environment. Half
an hour aer administraon of water or oil, rats were placed
in separate acvity cages to get familiar with the environment.
Numbers of cage crossings were monitored for 10 min. Home
cage acvity was monitored in a balanced design [11].
Open eld test: Open eld acvity test is used to assess
behavioral responses such as locomotor acvity and
exploraon in a novel environment. The apparatus consisted
of a square area (76 × 76 cm) with opaque walls 42 cm high.
The oor was divided into 25 equal squares (15 cm). One and a
half hour aer the administraon of water or oil, a single
animal was taken out from its home cage and placed in the
central square of the open eld. Latency period (s) to move
from the central square and number of squares crossed with
all four paws were recorded for a period of 5 min as reported
earlier [11,12]. Acvies of control and test groups were
monitroed in a balanced design to avoid order and me eect.
Elevated plus maze test: Elevated plus maze (EPM) model
was used to monitor animal’s natural behavior which is fear of
novel and open areas. Rats normally spend more me
exploring the enclosed elevated arm of a maze compared with
the open and exposed elevated arm. The anxiolyc eects of
ananxiety drugs have been determined by these typical
paerns of behavior. Rats treated with ananxiety drugs
generally spend more me in open elevated arms compared to
controls. Plus maze apparatus is used to assess the anxiogenic
or anxiolyc acvity of novel drugs. The maze consists of four
arms of equal size arranged in shape of ‘plus’ sign having 50
cm length and 10 cm width and elevated (at a height of 60 cm)
from the oor. Two opposite arms of the maze were open
while other two were closed joined together by the central
area of 10 × 10 cm. Closed arm contains 15 cm high side and
end walls. To monitor anxiolyc eect, three hour aer the
administraon of water or oil a single rat was placed in the
central area of the apparatus facing the corner between a
closed and an open arm. The me spent in open arm by the
animal was recorded for 5 min. Both water- and oil-treated
groups were tested in a balanced design to avoid order eect
[13].
Morris water maze test: Morris water maze test was
performed to study learning acquision and memory retenon
in rats as developed earlier [14]. The apparatus used for water
maze test was a white plasc circular tank with a diameter of
90 cm and height of 60 cm. Opaque milky water (24 ± 2°C) was
added in the pool to a depth of 30 cm. A square plaorm (10 ×
10 cm2) was submerged 2 cm below the water surface and
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posioned in a xed locaon (North quardrant) to provide an
escape from water for rats [15]. Water maze tank was placed
in a room surrounded by invariable visual cues (window,
cabinets, equipments, etc.) Which remained invariable with
the water maze during the enre experiment. Water maze was
arbitrarily divided into four equal quadrants (North, South,
East, and West). This test was performed aer ve weeks of
daily administraon of olive oil.
In the training phase, each animal was allowed in a specic
me to locate the hidden plaorm in three trials from three
dierent start posion, one from each quadrant (other than
the quadrant with hidden plaorm). During each trial, an
animal was placed in the water maze, facing the tank wall and
given 120 s to locate and climb onto the plaorm. The rat was
allowed to stay on the plaorm for 10 second. If it failed to
locate the plaorm within the allowed me it was guided
gently onto the hidden plaorm. Aer each trial, animal was
placed in a cage containing dry towel for 60 s before the next
trial.
In the test session, rats were tested for learning acquision
as well as memory retenon by placing the rat in the South
quadrant and monitoring me to reach the plaorm. Rats
were tested for learning acquision 2 hours aer the trial
phase between 12:30 and 13:30 h while memory retenon
was monitored next day between 9:30 and 10:30 h.
Analysis of anoxidant enzymes
Determinaon of MDA content: The procedure for
esmaon of lipid peroxidaon was performed as described
previously [16] with slight modicaons. An aliquot of 100 µL
plasma and 2 mL of 0.375% TBA in 15% TCA were thoroughly
mixed in test tubes. This mixture was placed in boiling water
for 20 min and allowed to cool in ice-cold water at 4°C. Aer
centrifugaon at 2,000 × g for 10 min (4°C), the resulng clear
supernatant of light pink color (250 µL) was collected and
transferred to 96-well microplate. The absorbance of the
supernatant was recorded at 532 nm in microplate absorbance
reader (SunriseTM, Tecan Trading AG, Switzerland). The
amount of TBA reactants was calculated using molar exncon
coecient of malondialdehyde (1.56 × 105). The data was
expressed as µmoles of MDA per liter of rat plasma.
Determinaon of GSH-Px acvity: GSH-Px acvity of plasma
was measured by the method of [17,18]. A mixture containing
30 µL of sodium phosphate buer (0.1 M, pH 7.4), 20 µL of
glutathione (2 mM), 30 µL of plasma, 10 µL of sodium azide
(10 mM), and 10 µL of hydrogen peroxide soluon (1 mM) in a
2 mL microcentrifuge tube was incubated for 15 min at 37°C.
The reacon was stopped by vigorously injecng a total of 50
µL 5% TCA. Aer centrifugaon at 8,325 rpm for 5 min (4°C),
the resulng supernatant (25 µL) was collected and transferred
to 96-well microplate. 50 µL of sodium phosphate buer (0.1
M, pH 7.4) and 175 µL of DTNB (1 mM) were added to
supernatant. The mixture was given a shake duraon of 10 s
by placing the 96-well microplate in the absorbance reader.
The absorbance was measured at 420 nm in microplate
absorbance reader (SunriseTM, Tecan Trading AG,
Switzerland). An appropriate control was run along each
plasma sample and its reacon was immediately stopped at 0
min. GSH-Px acvity was expressed as the µmoles of GSH
converted to GSSG per min per milliliter of rat plasma.
Neurochemical analysis of biogenic amines and
metabolites
Biogenic amines and metabolites were extracted as
reported earlier 19. 5 mes volume of the extracon medium
(containing sodium metabisulte (0.1%), perchloric acid (0.4
M), EDTA (0.01%), cysteine (0.01%) was added to the brain
ssue. Brain sample was homogenized (by using Ultra-Turrax
T8 homogenizer, IKA®-Werke, Germany) and centrifuged twice
at 12,000 rpm for 5 minutes at 4°C. Supernatants were
collected and injected (20 µL) to HPLC-ECD for simultaneous
measurements of DA, and 5-HT as well as their metabolites,
DOPAC, HVA, and 5-HIAA as previously reported [19,20]. A 5
µm ODS separaon column (0.6 × 250 mm) was used. 0.1 M
sodium phosphate buer (pH 2.9) containing methanol (10%),
EDTA (0.005%), and sodium octyl sulfate (0.023%) was used as
a mobile phase at an operang pressure of 2000-3000 psi on
HPLC pump (Shimadzu, Kyoto, Japan).
Electrochemical detecon was done at an operang
potenal of +0.8 to +1.0 V by using Schimadzu L-ECD-6A
detector. The individual components of sample as well as
standard were idened and quaned by comparing their
retenon mes and area under the peaks by using a soware
(Shimadzu’s LC soluon).
Stascal Analysis
Food intake, and body weight as well as home cage, open
eld, and elevated plus maze acvies were analyzed by one-
way analysis of variance (ANOVA), using IBM SPSS Stascs
(version 15.0). Post hoc comparison was done by Tukey’s test
and p-values less than 0.05 were taken as stascally
signicant.
Results
Eects of olive oil on food intake and body
weights
Eects of olive oil on food intake and percent change in
body weight are shown in Figure 1. Analysis of the data by
one-way ANOVA showed that the eects of oil treatment on
food intake (F (4,30)=2.125, p>0.05) and body weight (F
(4,30)=2.157, p>0.05) were not signicant.
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Figure 1: Eects of repeated administraon of olive oil (0.1 and 0.25 mL/kg) for ve weeks on food intake and body weight in
rats. Values are means ± SD (n=7). Dierence between groups by one-way ANOVA was not signicant.
Eects on home cage, open eld, and elevated
plus maze acvies
Eects of olive oil treatment on acvity in home cage, open
eld, and elevated plus maze performance are shown in
Figures 2 and 3.
Figure 2: Eects of repeated administraon of olive oil (0.1 and 0.25 mL/kg) for ve weeks on home cage and open eld
acvies in rats. Values are means ± SD (n=7). Signicant dierences by Tukey's test: *p<0.05 following one-way ANOVA.
Figure 3: Eects of repeated administraon of olive oil (0.1 and 0.25 mL/kg) aer 1 week and 5 weeks on elevated plus maze
acvies in rats. Values are means ± SD (n=7). Signicant dierences by Tukey's test: *p<0.05 following one-way ANOVA.
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Data analyzed using one-way ANOVA showed signicant
treatment eects on home cage (F (2,18)=35.489, p<0.01),
open eld (F (2,18)=24.992, p<0.01) and elevated plus maze
(aer 5 weeks treatment) (F(2,18)=15.064, p<0.01).
Eects on elevated plus maze (aer 1week treatment) (F
(2,18) =2.305, p>0.01) were not signicant. The post hoc
analysis by Tukey’s test showed a decrease of motor acvity in
the home cage.
Lower dose of olive oil increased exploratory acvity in open
eld as well as me spent by animals in open arm of plus maze
whereas higher dose of olive oil did not alter these.
These results suggest that both doses of olive oil
administered for ve weeks decreased motor behavior in the
familiar environment of acvity cage. Exploratory acvity in
open eld is increased by low dose of olive oil. An increase in
me spent in open arm showed ananxiety-like eect of low
dose of olive oil aer 5 weeks treatment.
Eects of olive oil on learning acquision and
memory retenon
Figure 4 shows eects of the olive oil treatment on water
maze performance.
Figure 4: Eects of repeated administraon of olive oil (0.1 and 0.25 mL/kg) for ve weeks on learning acquision and
memory retenon in rats. Values are means ± SD (n=7). Signicant dierences by Tukey's test: *p<0.01 following one-way
ANOVA.
Data analyzed using two-way ANOVA (repeated measure
design) showed signicant eects of repeated measure (F
(1,18) =10.045, 18; p<0.01), treatment (F (2,18) =12.415,
p<0.01), and interacon between repeated measure and
treatment (F (2,18)=10.209, p<0.01).
The post hoc analysis by Tukey’s test showed that
administraon of lower but not higher dose of olive oil
improved memory retenon. Eects of both doses of olive oil
on learning acquision were not signicant.
Eects of olive oil on anoxidant enzymes
Figure 5 shows eects of olive oil treatment on plasma MDA
levels and GSH-Px acvity.
Figure 5: Eects of repeated administraon of olive oil (0.1 and 0.25 mL/kg) f for ve weeks on malondialdehyde (MDA) and
glutathione peroxidase (GSH-Px) levels in rats. Values are means ± SD (n=7). Signicant dierences by Tukey's test: *p<0.05
following one-way ANOVA.
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Data analyzed using one-way ANOVA showed signicant
eects on MDA (F (2,18)=24.347, p<0.01) and GSH-Px (F
(2,18)=20.063, p<0.01). The post hoc analysis by Tukey’s test
showed that administraon of higher but not lower dose of
olive oil decreased MDA by 20%. While administraon of
lower but not higher dose of olive oil increased GSH-Px by
35%.
These results suggest that higher dose of olive oil produces
anoxidant eect by decreasing lipid peroxidaon. An increase
in GSH-Px enzyme acvity showed anoxidant eect of lower
dose of olive oil.
Eects of olive oil on biogenic amines and
metabolites
Eects of olive oil treatment on biogenic amines and their
metabolites are given in Table 1.
Table 1: Eects of 5 weeks administraon of olive oil on biogenic amines and their metabolites.
Parameters (ng/g) Water Olive 10 Olive 25
DA 726 ± 77 755 ± 66 625 ± 79
HVA 70 ± 13 271 ± 38** 120 ± 20**
DOPAC 67 ± 10 71 ± 11 78 ± 9
5-HT 528 ± 68 632 ± 54* 571 ± 60
5-HIAA 194 ± 45 221 ± 38 201 ± 18
* p<0.05, ** p<0.01 from water treated controls
Abbreviations: DA: Dopamine; DOPAC: Dihydroxyphenyl Acetic Acid; HVA: Homovanillic Acid; 5-HT: 5-hydroxytryptamine (serotonin); 5-HIAA: 5-Hydroxyindole
Acetic Acid; Olive 10 (0.1 mL/kg); Olive 25 (0.25 mL/kg).
Data analyzed using one-way ANOVA showed signicant
eects on HVA (F (2,18) =115.271, p<0.01), 5-HT (F (2,18)
=5.139, p<0.05), and DA (F (2,18)=5.892, p<0.05). Eects on
DOPAC (F (2,18) =1.865, p>0.05), and 5-HIAA (F (2,18) =1.073,
p>0.05) were not signicant. The post hoc analysis by Tukey’s
test showed that administraon of both doses of olive oil
increased HVA concentraon. Lower but not higher dose of
olive oil increased 5-HT concentraon. Administraon of olive
oil had no eect on DA concentraon.
Discussion
Eects of long term administraon of olive oil on brain DA
and 5-HT metabolism in relaon to anxiety, memory, motor
acvity, and anoxidant properes were monitored in the
present study. A consistent nding of this study is an increase
in HVA concentraon by both doses of olive oil. On the other
hand, 5-HT levels increased in low dose olive oil-treated
animals, but the increases were not signicant at higher dose.
Interesngly, enhancement in open eld exploraon and
ananxiety-like eects in elevated plus maze were also
produced at low doses only. Moreover, animals treated with
low dose olive oil exhibited improved performance in water
maze test. Both doses of olive oil exhibited an anoxidant
eects. However, treatment of the animals with low or high
doses of olive oil produced no eect on food intake and body
weight. The results suggest a potenal ananxiety and
nootropic eect of low dose of olive oil, and a role of DA as
well as 5-HT in these eects.
Other authors have reported that long term oral
administraon of extra-virgin olive oil (EVOO) enriched with
polyphenols (total polyphenolic concentraon of the original
EVOO: 210 mg/kg, gallic acid equivalent) improved
performance in T-maze test and object recognion task in
senescence-accelerated mouse-prone 8 (SAMP8) [7]. In the
present study, very low doses of pure olive oil were used. We
found that oral administraon of 0.1 mL/kg olive oil for 5
weeks improved performance in Morris water maze test
suggesng that long term intake of olive oil can improve
cognive performance (Figure 4).
Previous studies have explained the memory-enhancing
eects of enriched extra-virgin olive oil in terms of anoxidant
properes of acve components, including hydroxytyrosol,
tyrosol, oleuropein, deacetoxy-ligstroside aglycon, and
acetoxypinoresinol [7,21]. The present results of improved
performance in water maze at low but not high doses of olive
oil cannot be explained in terms of anoxidant eects of the
oil because anoxidant eects occurred at both doses (Figure
5). An increase in DA neurotransmission is also oen linked
with improved performance in Morris water maze test [22,23].
However, in the present study HVA levels also increased at
both doses of olive oil (Table 1). The present results on an
improved cognion at low but not high doses of olive oil
suggest that enhanced 5-HT neurotransmission at low doses is
possibly involved in the memory-enhancing eects of olive oil.
Indeed, an increase in 5-HT neurotransmission in tryptophan-
treated rats has been shown to improve performance in
Morris water maze test [24]. In the quest of why low but not
high doses are eecve in improving cognion, reducing
anxiety, and increase 5-HT metabolism, it is important to note
that a number of acve components have been isolated from
olive oil and only few of these have reported to increase
cognive properes [25]. It is also possible that some
components present in olive oil impair memory and are
eecve only at high doses. These components, if present, can
Journal of Nutraceuticals and Food Science
Vol.3 No.1:4
2018
6This article is available from: http://nutraceuticals.imedpub.com/

also mask memory-enhancing eects of reported memory-
enhancing components in the oil.
Other authors have shown an ananxiety as well as
andepressant eect of higher dose of olive oil administered
for 4 weeks, which was associated with a decrease in brain 5-
HT metabolism 6. A decrease in brain 5-HT metabolism
following 5 weeks administraon of high dose of olive oil did
not occur in the present study (Table 1). In general, the
present and previous ndings tend to suggest an increase or
decrease in brain 5-HT metabolism following long term
administraon of low or high dose of olive oil. In the quest of
why low but not high dose of olive oil increase brain 5-HT
metabolism, it is important to note that neurochemical eects
of acve component olive oil have not been explored. Further
studies may well explain why low but not high doses of olive
oil increase 5-HT metabolism. The mechanism by which olive
oil can increase brain 5-HT as well as DA metabolism also
requires further invesgaons.
An increase in exploratory acvity in open eld by olive oil
has been reported previously [26] and in the present study
(Figure 2b). Addionally, we found a decrease in acvity in the
familiar environment (Figure 2a). Benzodiazepines decrease
anxiety in open eld. Convenonal anxiolycs like diazepam
increase acvity in open eld. Olive oil has anxiolyc-like eect
similar to benzodiazepines. Benzodiazepines at low dose
decrease acvity in the familiar environment [27] and increase
acvity in novel environment. This study also showed that low
but not high dose is anxiolyc.
Conclusion
In conclusion, the present results tend to suggest that
together with anoxidant properes, low dose of olive oil also
produces ananxiety and memory-enhancing eect.
Neurochemical studies on the eects of acve components in
olive oil may help to explain the mechanisms involved in its
ananxiety and/or nootropic eects of olive oil. At least some
of its more acve components seem promising candidates for
treang anxiety and memory decits.
Acknowledgements
The authors are thankful to director Dr. Panjwani Center for
Molecular Medicine and Drug Research, Internaonal Center
for Chemical and Biological Sciences (ICCBS), University of
Karachi, Karachi for providing faculty research grants.
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