Effects of the Agents Influencing the Serotonergic and Cannabinoid Systems on Memory in the Avoidance Test in Mice
Adult male albino mice in a shuttle box system were used for examination of learning for avoidance behavior and its deactivation. We measured the step-through latency in the acquisition of the task (STLa) before injections of the drugs tested (fluoxetine and URB597 (a serotonin reuptake inhibitor...
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Інститут фізіології ім. О.О. Богомольця НАН України
2014
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| Cite this: | Effects of the Agents Influencing the Serotonergic and Cannabinoid Systems on Memory in the Avoidance Test in Mice / N. Rezapoor, S. Shahidi, A. Komaki // Нейрофизиология. — 2014. — Т. 46, № 2. — С. 134-140. — Бібліогр.: 37 назв. — англ. |
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| author | Rezapoor, N. Shahidi, S. Komaki, A. |
| author_facet | Rezapoor, N. Shahidi, S. Komaki, A. |
| citation_txt | Effects of the Agents Influencing the Serotonergic and Cannabinoid Systems on Memory in the Avoidance Test in Mice / N. Rezapoor, S. Shahidi, A. Komaki // Нейрофизиология. — 2014. — Т. 46, № 2. — С. 134-140. — Бібліогр.: 37 назв. — англ. |
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| description | Adult male albino mice in a shuttle box system were used for examination of learning
for avoidance behavior and its deactivation. We measured the step-through latency in the
acquisition of the task (STLa) before injections of the drugs tested (fluoxetine and URB597
(a serotonin reuptake inhibitor, SSRI, and an agent preventing decomposition of endocannabinoids, respectively) and the respective latency 24 h later after injections of these
agents (STLr); total time spent in the dark compartment (TDC) was also measured in these
situations. In mice that received fluoxetine (5, 10, and 20 mg/kg), the STLr were longer than
those in the control, and the difference was significant at 10 mg/kg. Injections of URB597
decreased the STLr and, at medium and high doses (0.3 and 1.0 mg/kg), provided significant
differences. All doses of fluoxetine led to significant decreases in the TDC values, while
injections of URB597 increased this index (at 0.3 and 1.0 mg/kg, the shifts were significant).
Combined injections of fluoxetine and URB597 (5 + 0.1, 10 + 0.3, and 20 + 1.0 mg/kg)
increased the STLr values and decreased TDC values to the levels comparable with those at
isolated injections of fluoxetine in the respective doses. Thus, fluoxetine improved memory,
while URB597 impaired it; fluoxetine is capable of nullifying negative effects of URB597.
У дорослих білих мишей-самців досліджували навчання
поведінці уникання та деактивацію цього процесу в
системі із човниковою камерою. Виміряли латентні
періоди перетину межі при навчанні дó ін’єкції тестованих
агентів – флуоксетину (інгібітора зворотного захоплення
серотоніну, SSRS) та URB597 (речовини, що перешкоджає
декомпозиції ендоканабіноїдів) і після таких ін’єкцій
(STLa і STLr) відповідно; визначали також загальний час,
проведений у темному компартменті в даних ситуаціях
(TDC). У мишей, які отримували флуоксетин (5, 10
або 20 мг/кг), STLr ставали більшими, ніж у контролі,
причому в разі використання 10 мг/кг різниця середніх
була вірогідною. Ін’єкції URB597 зменшували значення
TDC, і при середніх і високих дозах (0.3 і 1.0 мг/кг)
відмінності перевищували рівень вірогідності. Флуоксетин
у всіх дозах зумовлював істотне зменшення значень TDC,
а ін’єкції URB597 збільшували цей показник (при 0.3
та 1.0 мг/кг зрушення були вірогідними). Комбіновані
ін’єкції флуоксетину та URB597 (5 + 0.1, 10 + 0.3 і 20 +
+ 1.0 мг/кг) призводили до збільшення значень STLr
і зменшення TDC до рівнів, порівнянних із тими, які
спостерігалися в умовах ізольованих уведень флуоксетину
у відповідних дозах. Таким чином, флуоксетин покращував
пам’ять, тоді як URB597 порушував її; флуоксетин має
здатність нейтралізувати негативні ефекти URB597.
|
| first_indexed | 2025-12-02T01:25:31Z |
| format | Article |
| fulltext |
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2014.—T. 46, № 2134
UDC 612.821.2+612.833
N. REZAPOOR1, S. SHAHIDI1, and A. KOMAKI1
EFFECTS OF THE AGENTS INFLUENCING THE SEROTONERGIC
AND CANNABINOID SYSTEMS ON MEMORY
IN THE AVOIDANCE TEST IN MICE
Received May 10, 2013.
Adult male albino mice in a shuttle box system were used for examination of learning
for avoidance behavior and its deactivation. We measured the step-through latency in the
acquisition of the task (STLa) before injections of the drugs tested (fluoxetine and URB597
(a serotonin reuptake inhibitor, SSRI, and an agent preventing decomposition of endo-
cannabinoids, respectively) and the respective latency 24 h later after injections of these
agents (STLr); total time spent in the dark compartment (TDC) was also measured in these
situations. In mice that received fluoxetine (5, 10, and 20 mg/kg), the STLr were longer than
those in the control, and the difference was significant at 10 mg/kg. Injections of URB597
decreased the STLr and, at medium and high doses (0.3 and 1.0 mg/kg), provided significant
differences. All doses of fluoxetine led to significant decreases in the TDC values, while
injections of URB597 increased this index (at 0.3 and 1.0 mg/kg, the shifts were significant).
Combined injections of fluoxetine and URB597 (5 + 0.1, 10 + 0.3, and 20 + 1.0 mg/kg)
increased the STLr values and decreased TDC values to the levels comparable with those at
isolated injections of fluoxetine in the respective doses. Thus, fluoxetine improved memory,
while URB597 impaired it; fluoxetine is capable of nullifying negative effects of URB597.
Keywords: serotonin, endocannabinoids, inhibitory avoidance test, acquisition,
retention, memory.
1Neurophysiology Research Center, Hamadan University of Medical Sciences,
Hamadan, Iran.
Correspondence should be addressed to
N. Rezapoor (e-mail: nastaranrezapoor@yahoo.com),
S. Shahidi (e-mail: siamakshahidi@yahoo.com, shahidi@umsha.ac.ir), or
A. Komaki (e-mail: alirezakomaki@gmail.com, komaki@umsha.ac.ir).
INTRODUCTION
Serotonin is one of the most important neurotransmitters
involved in the memory and learning processes [1].
Cannabinoids also play important roles in the control
of neurobehavioral phenomena [2]. The relationship
between cannabinoids and the memory system was
examined in a few studies. It was reported that
endocannabinoids (like anandamide) impair learned
behavior [3]. At the same time, another study showed
improvement in cognition and memory under the
influence of these agents [2]. The serotonin system
affecting the memory structures plays an important
role in mood disorders and dysfunction of serotonergic
neurotransmission in various mental diseases [4]. This
is why serotonin reuptake inhibitors (SSRIs) are most
frequently used in the treatment of major depression [5].
We used fluoxetine as one of the SSRIs in the current
study. This agent demonstrated no binding affinity in
the brain for any other major receptor classes, and it
is characterized by a relatively long half-life in the rat
[6]. There are, however, some reports that serotonin
(5-HT) providing activation of 5-HT receptors impaired
short-term memory, and blocking of the respective
effects may intensify the antidepressant effect of
SSRIs and improve cognition [7]. It was reported that
fluoxetine improved cognition and spatial memory
[5], but some results are contradictory [8, 9].
Type 1-cannabinoid receptors (CB1) and 5-HT
receptors are distributed in the hippocampus, and
both of them exert effects on the memory and learning
functions. Thus, it was suggested that their combined
activation may affect learning and memory in a
complex mode [10]. This aspect has not been studied
well until now. So, we decided to study the effects
of combined potentiation of the effects of endogenous
serotonergic and cannabinoid systems on memory in
mice.
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2014.—T. 46, № 2 135
EFFECTS OF THE AGENTS INFLUENCING THE SEROTONERGIC
METHODS
Animals. Male albino mice (body mass 20-30 g) were
used in this study. The animals were housed five per
cage and maintained at 20 ± 2°C and at a 12/12-h light/
dark photocycle (lights on 07:00 a.m.). Water and food
were available ad libitum. All mice were acclimatized
to the environment for at least 10 days prior to the start
of behavioral testing. They were trained to perform
the step-through inhibitory avoidance task (IAT). The
mice received single intraperitoneal (i.p) injections of
saline, fluoxetine (5.0, 10, or 20 mg/kg), URB597 (0.1,
0.3, or 1.0 mg/kg), or of their combination (fluoxetine
+ URB597, 5 + 0.1, 10 + 0.3, or 20 + 1.0 mg/kg). After
this, their retention of the memory performance was
evaluated.
Inhibitory Avoidance Apparatus. The apparatus
and procedure were basically the same as those in
our previous studies [11-13]. The apparatus consisted
of a lighted chamber and a dark one. Between two
chambers, there was a rectangular opening that could
be closed by an opaque guillotine door. The floor of
both chambers was equipped with stainless steel rods,
and the floor of the dark chamber could be electrified.
Mice were placed in a lighted compartment of the
apparatus facing away from the door; 5 sec later, the
guillotine door was raised. Once the mouse entered
the dark compartment, the door was closed, and the
mouse was taken from the dark compartment into
its home cage. The habituation trial was repeated 30
min later and followed (after the same interval) by
the first acquisition trial. The entry latency to the
dark compartment (step-through latency, STL) was
recorded when the animal had placed all four paws
on the floor of the dark compartment. After an animal
spontaneously entered the dark compartment, the
guillotine door was lowered, and a mild electrical
shock (0.6 mA) was applied for 3 sec. The mouse was
retained in the apparatus and received a foot-shock
each time the animal re-entered the dark compartment.
Training was terminated when the mice remained in
the light compartment for consecutive 120 sec.
Experimental Procedures. The animals were
divided into 10 groups (n = 8 in each). They were
trained for the step-through IAT. The STL of the
first acquisition trial and the number of trials to IAT
acquisition were recorded.
The retention test was performed 24 h after the
IAT acquisition trial. The animals received single
i.p injections of the above-mentioned agents 30 min
before the retention test. Then, each mouse was placed
in a lighted chamber as in the IAT training; 5 sec later,
the guillotine door was raised. Then, the STL and time
spent in the dark compartment (TDC) were recorded
up to 300 sec. If the mouse did not enter the dark
compartment within this time interval, the retention
test was terminated, and a ceiling score of 300 sec was
assigned.
Statistical Analysis. Statistical significance
of the differences of each measured parameter
between experimental groups was estimated by one-
way ANOVA or Kruskal–Wallis non-parametric
ANOVA and followed by the Tukey or Dunn tests for
multigroup comparison when appropriate. The zero
hypothesis probabilities below 0.05 were considered
significant. All data presented in the figures are given
as means ± s.e.m.
RESULTS
Acquisition. There were neither significant difference
in the number of trials to acquisition nor in the STL
in the acquisition of the task (STLa) between the
experimental groups. There was also no difference
in the mean body mass among all groups (P > 0.05;
Fig. 1).
Retention. In the retention test done 24 h after the
training period, the one-way ANOVA test indicated that
there was a significant difference in the STL (STLr)
values between the experimental groups (Fig. 2). The
Tukey post-hoc test revealed that the STLr in the
fluoxetine (10 mg/kg)-treated group was significantly
longer than that in the control (P < 0.05). The values
of STLr in the URB597 (0.3 and 1.0 mg/kg)-injected
groups were significantly shorter in comparison with
the control (P < 0.05 and P < 0.01, respectively). In
the three (fluoxetine + URB597)-treated groups, the
STLr values were significantly longer than those in the
control (P < 0.05).
Statistical comparison of the TDC by one-way
ANOVA indicated that there was a significant
difference between experimental groups (Fig. 2). The
Tukey post-hoc test showed that, in the fluoxetine
(5, 10, and 20 mg/kg)-treated groups, the TDCs were
highly significantly shorter than those in the control
(P < 0.01, P < 0.001, and P < 0.01, respectively).
On the other hand, in the URB597 (0.3 and
1.0 mg/kg) mice, the TDCs were much longer than
those in the control (P < 0.001). At the same time,
injections of fluoxetine+URB597 in all the three
combinations used led to highly significant (P < 0.001)
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2014.—T. 46, № 2136
N. REZAPOOR, S. SHAHIDI, and A. KOMAKI
0
1
2
3
Contr. F5 F10 F20 U0.1 U0.3 U1
F5+U0.1
F10+U0.3
F20+U1
0
10
20
30
Contr. F5 F10 F20 U0.1 U0.3 U1
F5+U0.1
F10+U0.3
F20+U1
0
10
20
30
40
Contr. F5 F10 F20 U0.1 U0.3 U1
F5+U0.1
F10+U0.3
F20+U1
A
A
Bsec
secsec
g
B
C
F i g. 1. Number of trials to inhibitory avoidance test acquisition
(A), step-through latency in acquisition trials, sec (B), and body
mass of the mice, g (C) in all experimental groups. Columns
show means ± s.e.m. *P < 0.05, **P < 0.01, and ***P < 0.001,
as compared with the control group. F5, 10, and 20 are doses of
fluoxetine, respectively, 5, 10, and 20 mg/kg; U0.1, 0.3, and 1.0 are
doses of URB597, respectively, 0.1, 0.3, and 1.0 mg/kg; Contr. is
the control.
Р и с. 1. Кількість реалізацій при тренуванні в тесті гальмівного
уникання (А), латентних періодів (с) переходу межі в перебігу
тренування (B) та маси тіла мишей (г) в усіх експериментальних
групах (С).
*
** *
** * *
0
50
100
150
200
250
300
350
Contr. F5 F10 F20 U0.1 U0.3 U1
F5+U0.1
F10+U0.3
F20+U1
***
*** ***
***
***
*** *** ***
-50
0
50
100
150
200
250
300
Contr. F5 F10 F20 U0.1 U0.3 U1
F5+U0.1
F10+U0.3
F20+U1
F i g. 2. Values of the step-through latency in the retention test, sec (A) and total time spent in the dark compartment, sec (B) in all
experimental groups. Other designations are the same as in Fig. 1.
Р и c. 2. Значення латентних періодів (с) переходу межі у відставленому тесті (А) та загального часу (с), проведеного в темному
відсіку (B) в усіх експериментальних групах.
shortenings of TDCs to the levels close to those in the
“pure” fluoxetine-injected groups.
DISCUSSION
Different neurotransmitters are involved in the memory
and learning processes, and one of the important
ones, from this aspect, is serotonin [1]. On the other
hand, cannabinoids also play important roles in the
neurobehavioral processes [2]. The cannabinergic
system components, such as its ligands and receptors
(CB1s), are distributed in the hippocampus and other
structures related to memory; it is well known that
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2014.—T. 46, № 2 137
EFFECTS OF THE AGENTS INFLUENCING THE SEROTONERGIC
the hippocampus is an important center for learning
and memory formation. Type 1-cannabinoid receptors
are present in presynaptic terminals of neurons of the
hippocampus and striatal complex [14].
Our study showed that the STLr values (STL of
going to the dark compartment after injections of
URB597 and fluoxetine) 24 h after the task (IAT)
acquisition in groups that received moderate (0.3
mg/kg) and high doses (1.0 mg/kg) of URB597
were significantly shorter than in the control
(P < 0.05). The TDC values altogether (at low,
0.1 mg/kg, moderate, 0.3 mg/kg, and high 1.0 mg/kg
doses of URB597) were greater than in the control
group (P < 0.001), suggesting that endocannabinoids
significantly impair memory processing. There are
different and controversial communications with
respect to the effects of cannabinoids on memory and
learning processing. At the same time, it was reported
that exogenous cannabinoids disrupt encoding in the
process of memorization by altering the functions
of a specific type of hippocampal neurons [15],
and that endocannabinoids exert a negative effect
on the hippocampus-related encoding for short-
term memory [15]. In our study, a negative effect of
cannabinoids on memory is consistent with earlier
reports. Administration of a cannabinoid antagonist
SR (SR14176A) attenuated the memory impairment
caused by anandamide and improved memory and
learning [16]. Local administration of SR (SR14176A)
in the delayed radial maze task caused the blockade
of CB1 receptors and enhanced consolidation of
spatial memory [17]. Another study reported that
endocannabinoids impaired memory and caused
extinction of previously trained behavior [3]. Studies
on CB1-knockout mice in the objective recognition
task showed that these animals demonstrated better
memory than the wild-type control; spatial memory
was facilitated [18]. In other studies, it was described
that administration of a CB1 antagonist (AM251)
provided the blockade of extinction of memory,
improvement of the performance related to short-term
memory, facilitation of memory, and reversion of the
cognition deficits caused by cannabinoid agonists [16,
19, 20]. All the above reports agree with our results.
Nonetheless, it should be mentioned that we found
some reports that are in contrast. As was reported
earlier, administration of a cannabinoid antagonist
impaired the spatial learning function [21], and a CB1
receptor antagonist negatively influenced memory in
certain tests [22].
The serotonergic system, by acting via the
prefrontal cortex, dorsal hippocampus, and amygdalar
complex [23], plays important roles in mood disorders.
Dysfunction of serotonergic neurotransmission
induces various mental disorders [4]; thus, SSRIs
became the most frequently used agents for treatment
of major depression [5]. The SSRIs increased the
amount of 5-HT receptors. The effect of 5-HT can be
explained by its high level in brain structures involved
in cognition (hippocampus and temporal cortex) [24,
25]. The 5-HT receptor overactivation impaired short-
term memory, and blocking of these receptors may
improve the antidepressive effect of SSRI and enhance
cognition [7].
Our results showed that the STLr value after
injections of URB597 and fluoxetine into the animal
group that received a moderate dose of fluoxetine (10
mg/kg) was longer than that in the control group; the
analogous trend was observed in other fluoxetine-
injected groups. In all three groups that received low
(5 mg/kg), moderate (10 mg/kg), and high (20 mg/
kg) doses of fluoxetine, the TDCs were shorter than
in the control group suggesting an improvement effect
on the memory function by fluoxetine. Most studies
reported comparable results. Fluoxetine improved
cognition and spatial memory, and SSRIs partly
removed memory deficits in patients with various
pathological conditions [5, 26]. At the same time,
some reports are in contrast with our findings [27].
Fluoxetine was reported to impair different types of
memory and cognition in patients with various mental
disorders [8, 28, 29]; so, there are some contradictions
also in this field. Therefore, the mechanisms of the
actions of the serotonergic system and cannabinoids
and their effects on memory processing and learning
remain incompletely identified. Fluoxetine increased
neurogenesis in the hippocampus and other regions
associated with cognition and memory [30].
We found clear indications that the serotonergic
system and endocannabinoid system may provide
combined e ffec t s . Endocannabino ids a ffec t
serotonergic neurons [10]. On the other hand, CB1
and 5-HT receptors are present in the hippocampus,
and it seems that their combined activation can
affect memory and learning in a complex mode [31].
Fluoxetine increases the amount of CB1s in the
hippocampus and, thus, can modify the cannabinoid
system [32].
This aspect (combined action of fluoxetine and
cannabinoids on memory) was not investigated until
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2014.—T. 46, № 2138
N. REZAPOOR, S. SHAHIDI, and A. KOMAKI
now. This in why we studied the effects of both these
factors in the groups that received fluoxetine and
URB597 together. Our results showed that the STLr
values in all “mixed” groups (5 mg/kg fluoxetine +
+ 0.1 mg/kg URB597, 10 mg/kg fluoxetine +
+ 0.3 mg/kg URB597, and 20 mg/kg fluoxetine +
+ 1.0 mg/kg URB597) were longer (P < 0.05) than in
the control group. At the same time, the TDCs in all
“mixed” groups were shorter than those in the control
(P < 0.001), suggesting that fluoxetine abolished
negative effects of endocannabinoids on memory.
How serotonin affects the cannabinoid system? We
suggest that serotonin can do this via its interaction
with the dopaminergic and glutaminergic systems
[1, 33-35]. On the other hand, fluoxetine can increase
the number of CB1 receptors in the hippocampus, and
the serotonergic system can modify the cannabinoid
system [32]; thus, the serotonergic and cannabinoid
systems may affect each other via this mechanism.
Other reports may help us to understand the
mechanism of such combined activation in memory
processing; endocannabinoids have a nerve-protective
effect and promote neuronal proliferation. Both the
above systems affect neuronal differentiation in the
hippocampus and other structures related to memory
[7, 23, 36, 37].
Our study showed how the serotonergic system can
improve memory; on the other hand, cannabinoids
can impair memory. It can be concluded that the
serotonergic system nullifies the negative effects of
cannabinoids on memory.
Our study has some limitations. For example, we
did not study the effects of the above systems on
neurogenesis and on other related cerebral phenomena.
We suggest, however, that some obtained information
may help one to identify in more detail the mechanisms
of interaction between the serotonergic system and
cannabinoids in future studies.
Based on our own research, we believe that there
is a need for further study to determine the combined
potential effect of endogenous serotonergic and
cannabinoid systems on memory.
Acknowledgments. This work was endorsed and
supported by the Hamadan University of Medical Sciences
(Iran). The authors wish to thank Mojgan Rezaei (BSN-CRN,
Certified Registered Nurse) and Jakiann Mork (MSN-ANCC,
Gerontological Nurse Practitioner) from the University of
Minnesota Medical Center Fairview and also Ali Rezaei from
the Texas Tech University for scientific comments and editing
of the manuscript.
All experimental procedures corresponded to internationally
accepted ethical principles for scientific experiments on
vertebrate animals.
The authors, N. Rezapoor, S. Shahidi, and A. Komaki,
confirm that they have no conflict of interests.
Н. Резапур1, С. Шахіді1, А. Комаки1
ВПЛИВИ АГЕНТІВ, ДІЮЧИХ НА СЕРОТОНІНЕРГІЧНУ
І КАНАБІНОЇДНУ СИСТЕМИ, НА ФОРМУВАННЯ
ПАМ’ЯТІ В ТЕСТІ УНИКАННЯ У МИШЕЙ
1 Нейрофізіологічний дослідний центр при Хамаданському
медичному університеті (Іран).
Р е з ю м е
У дорослих білих мишей-самців досліджували навчання
поведінці уникання та деактивацію цього процесу в
системі із човниковою камерою. Виміряли латентні
періоди перетину межі при навчанні дó ін’єкції тестованих
агентів – флуоксетину (інгібітора зворотного захоплення
серотоніну, SSRS) та URB597 (речовини, що перешкоджає
декомпозиції ендоканабіноїдів) і після таких ін’єкцій
(STLa і STLr) відповідно; визначали також загальний час,
проведений у темному компартменті в даних ситуаціях
(TDC). У мишей, які отримували флуоксетин (5, 10
або 20 мг/кг), STLr ставали більшими, ніж у контролі,
причому в разі використання 10 мг/кг різниця середніх
була вірогідною. Ін’єкції URB597 зменшували значення
TDC, і при середніх і високих дозах (0.3 і 1.0 мг/кг)
відмінності перевищували рівень вірогідності. Флуоксетин
у всіх дозах зумовлював істотне зменшення значень TDC,
а ін’єкції URB597 збільшували цей показник (при 0.3
та 1.0 мг/кг зрушення були вірогідними). Комбіновані
ін’єкції флуоксетину та URB597 (5 + 0.1, 10 + 0.3 і 20 +
+ 1.0 мг/кг) призводили до збільшення значень STLr
і зменшення TDC до рівнів, порівнянних із тими, які
спостерігалися в умовах ізольованих уведень флуоксетину
у відповідних дозах. Таким чином, флуоксетин покращував
пам’ять, тоді як URB597 порушував її; флуоксетин має
здатність нейтралізувати негативні ефекти URB597.
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|
| id | nasplib_isofts_kiev_ua-123456789-148264 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 0028-2561 |
| language | English |
| last_indexed | 2025-12-02T01:25:31Z |
| publishDate | 2014 |
| publisher | Інститут фізіології ім. О.О. Богомольця НАН України |
| record_format | dspace |
| spelling | Rezapoor, N. Shahidi, S. Komaki, A. 2019-02-17T19:25:00Z 2019-02-17T19:25:00Z 2014 Effects of the Agents Influencing the Serotonergic and Cannabinoid Systems on Memory in the Avoidance Test in Mice / N. Rezapoor, S. Shahidi, A. Komaki // Нейрофизиология. — 2014. — Т. 46, № 2. — С. 134-140. — Бібліогр.: 37 назв. — англ. 0028-2561 https://nasplib.isofts.kiev.ua/handle/123456789/148264 612.821.2+612.833 Adult male albino mice in a shuttle box system were used for examination of learning for avoidance behavior and its deactivation. We measured the step-through latency in the acquisition of the task (STLa) before injections of the drugs tested (fluoxetine and URB597 (a serotonin reuptake inhibitor, SSRI, and an agent preventing decomposition of endocannabinoids, respectively) and the respective latency 24 h later after injections of these agents (STLr); total time spent in the dark compartment (TDC) was also measured in these situations. In mice that received fluoxetine (5, 10, and 20 mg/kg), the STLr were longer than those in the control, and the difference was significant at 10 mg/kg. Injections of URB597 decreased the STLr and, at medium and high doses (0.3 and 1.0 mg/kg), provided significant differences. All doses of fluoxetine led to significant decreases in the TDC values, while injections of URB597 increased this index (at 0.3 and 1.0 mg/kg, the shifts were significant). Combined injections of fluoxetine and URB597 (5 + 0.1, 10 + 0.3, and 20 + 1.0 mg/kg) increased the STLr values and decreased TDC values to the levels comparable with those at isolated injections of fluoxetine in the respective doses. Thus, fluoxetine improved memory, while URB597 impaired it; fluoxetine is capable of nullifying negative effects of URB597. У дорослих білих мишей-самців досліджували навчання поведінці уникання та деактивацію цього процесу в системі із човниковою камерою. Виміряли латентні періоди перетину межі при навчанні дó ін’єкції тестованих агентів – флуоксетину (інгібітора зворотного захоплення серотоніну, SSRS) та URB597 (речовини, що перешкоджає декомпозиції ендоканабіноїдів) і після таких ін’єкцій (STLa і STLr) відповідно; визначали також загальний час, проведений у темному компартменті в даних ситуаціях (TDC). У мишей, які отримували флуоксетин (5, 10 або 20 мг/кг), STLr ставали більшими, ніж у контролі, причому в разі використання 10 мг/кг різниця середніх була вірогідною. Ін’єкції URB597 зменшували значення TDC, і при середніх і високих дозах (0.3 і 1.0 мг/кг) відмінності перевищували рівень вірогідності. Флуоксетин у всіх дозах зумовлював істотне зменшення значень TDC, а ін’єкції URB597 збільшували цей показник (при 0.3 та 1.0 мг/кг зрушення були вірогідними). Комбіновані ін’єкції флуоксетину та URB597 (5 + 0.1, 10 + 0.3 і 20 + + 1.0 мг/кг) призводили до збільшення значень STLr і зменшення TDC до рівнів, порівнянних із тими, які спостерігалися в умовах ізольованих уведень флуоксетину у відповідних дозах. Таким чином, флуоксетин покращував пам’ять, тоді як URB597 порушував її; флуоксетин має здатність нейтралізувати негативні ефекти URB597. This work was endorsed and supported by the Hamadan University of Medical Sciences (Iran). The authors wish to thank Mojgan Rezaei (BSN-CRN, Certified Registered Nurse) and Jakiann Mork (MSN-ANCC, Gerontological Nurse Practitioner) from the University of Minnesota Medical Center Fairview and also Ali Rezaei from the Texas Tech University for scientific comments and editing of the manuscript. en Інститут фізіології ім. О.О. Богомольця НАН України Нейрофизиология Effects of the Agents Influencing the Serotonergic and Cannabinoid Systems on Memory in the Avoidance Test in Mice Впливи агентів, діючих на серотонінергічну і канабіноїдну системи, на формування пам’яті в тесті уникання у мишей Article published earlier |
| spellingShingle | Effects of the Agents Influencing the Serotonergic and Cannabinoid Systems on Memory in the Avoidance Test in Mice Rezapoor, N. Shahidi, S. Komaki, A. |
| title | Effects of the Agents Influencing the Serotonergic and Cannabinoid Systems on Memory in the Avoidance Test in Mice |
| title_alt | Впливи агентів, діючих на серотонінергічну і канабіноїдну системи, на формування пам’яті в тесті уникання у мишей |
| title_full | Effects of the Agents Influencing the Serotonergic and Cannabinoid Systems on Memory in the Avoidance Test in Mice |
| title_fullStr | Effects of the Agents Influencing the Serotonergic and Cannabinoid Systems on Memory in the Avoidance Test in Mice |
| title_full_unstemmed | Effects of the Agents Influencing the Serotonergic and Cannabinoid Systems on Memory in the Avoidance Test in Mice |
| title_short | Effects of the Agents Influencing the Serotonergic and Cannabinoid Systems on Memory in the Avoidance Test in Mice |
| title_sort | effects of the agents influencing the serotonergic and cannabinoid systems on memory in the avoidance test in mice |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/148264 |
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