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The efficacy of escitalopram, a pharmaceutical antidepressant, and exercise, a lifestyle intervention, in mitigating depressive symptoms has been established. This study investigated the impact of varying doses of escitalopram and the combination of forced exercise with escitalopram on stress-induced depressive-like behavior in male rats.

 Sixty-four male rats were allocated into eight groups: control (Co), sham (Sh), depression without treatment (Dep-WT), depression with exercise (Dep-Exe), depression with escitalopram at 10 mg/kg (Dep-Esc10), depression with escitalopram at 20 mg/kg (Dep-Esc20), depression with escitalopram at 10 mg/kg combined with exercise (Dep-Esc10-Exe), and depression with escitalopram at 20 mg/kg combined with exercise (Dep-Esc20-Exe). To induce depression, chronic restraint stress was administered for 6 hours per day over a period of 14 days.Following the stress induction period, rats were administered escitalopram (at doses of 10 or 20 mg/kg, i.p), subjected to treadmill running (20-21 m/min for 1 h/day), or subjected to a combination of both interventions. Depressive-like behaviour induced by stress and locomotor activity were assessed using the forced swimming test (FST) and the open field test (OFT), respectively.

 In the FST, the immobility time significantly increased in the Dep-WT, Dep-Exe, and Dep-Esc10 groups, while it significantly decreased in the Dep-Esc20, Dep-Esc10-Exe, and Dep-Esc20-Exe groups compared to the Dep-WT group. In the OFT, the central time and total travelled distance significantly decreased in the Dep-WT group. Conversely, central time significantly increased in the Dep-Esc10-Exe and Dep-Esc20-Exe groups, and all treatment groups exhibited a significant increase in central time compared to the Dep-WT group.

The findings suggest that combining exercise with escitalopram yields additive effects, representing a promising treatment protocol for anxiety, depression, and locomotor activity.

Light-dark cycles regulate the body’s physiological activity; hence, marked changes in these cycles could lead to conditions with impaired brain functions and disrupted moods (e.g., stress). Therefore, this study compared the impact of stress due to various photoperiodic durations on anxiety-like behavior, learning, memory, locomotor activity and memory consolidation in rats.

Thirty-five male rats were divided into five groups with different light(L)-dark(D) cycles: L20/D4, L16/D8, L12/D12 (control), L8/D16 and L4/D20 groups. After14 days, the elevated plus-maze (EPM) and passive avoidance (PA) tests were performed to assess the anxiety-like behaviors and brain functions.

The percentage of spent time, number of entries to the open arm of the EPM test and the entrance latency to the dark room of the PA test decreased significantly in the L20/D4 and L4/D20 groups; however, the reduction of latency to enter the dark room was particularly significant in the L20/D4 group. In addition, there were significant differences between the initial latency and latency after one day (as learning) in all experimental groups. The total dark stay time increased significantly in different photoperiods.

An abnormal light-dark length could disrupt certain brain functions, such as learning, memory, locomotor activity, memory consolidation and anxiety-like behavioral responses at different levels in a time-independent manner. The light-dark length (both minimum and especially the maximum day length) led to increased learning impairment and memory deficits, as well as worsened anxiety-like behaviors. The memory consolidation was also disrupted with various photoperiods.

The lateral habenula (LHb), a key area in the regulation of the reward system, exerts a major influence on midbrain neurons. It has been shown that the gamma-aminobutyric acid (GABA)- ergic system plays the main role in morphine dependency. The role of GABA type B receptors (GABABRs) in the regulation of LHb neural activity in response to morphine, remains unknown. In this study, the effect of GABABRs blockade in response to morphine was assessed on the neuronal activity in the LHb.

Experimental approach: 

The baseline firing rate was recorded for 15 min, then morphine (5 mg/kg; s.c) and phaclofen (0, 0.5, 1, and 2 µg/rat), a GABABRs’ antagonist, were microinjected into the LHb. Their effects on firing LHb neurons were investigated using an extracellular single-unit recording in male rats. Findings/

The results revealed that morphine decreased neuronal activity, and GABABRs blockade alone did not have any effect on the neuronal activity of the LHb. A low dose of the antagonist had no significant effect on neuronal firing rate, while blockade with doses of 1 and 2 µg/rat of the antagonist could significantly prevent the inhibitory effects of morphine on the LHb neuronal activity.

Conclusion and implications:

 This result indicated that GABABRs have a potential modulator effect, in response to morphine in the LHb.

Administration of antidepressants and exercise are among the therapeutic approaches to chronic stress. Therefore, this study compared the therapeutic effects of different doses of escitalopram, exercise, and exercise-accompanied escitalopram on synaptic potency and long-term plasticity in the hippocampal CA1 area in rats under chronic restraint stress.

The rats were allocated to different groups. The chronic restraint stress (6 hr/day) continued for 14 days. Injection of escitalopram (10 and 20 mg/kg) and treadmill running (1 hr/day) were performed after the stress induction. The input/output (I/O) functions and LTP induction were evaluated in the hippocampal CA1 area.

The fEPSP slope and amplitude after the LTP induction significantly decreased in the chronically stressed group. However, the serum corticosterone levels had significant enhancement in this group. In addition to serum corticosterone levels, the fEPSP slope and amplitude after the LTP induction were enhanced by exercise, escitalopram 20 mg/kg alone, and exercise-accompanied escitalopram 10 and/or 20 mg/kg in chronically stressed groups.

Overall, chronic stress impaired synaptic potency and long-term plasticity. These impairments were effectively reversed by exercise, escitalopram 20 mg/kg alone, and exercise-accompanied escitalopram 10 and 20 mg/kg. However, escitalopram 10 mg/kg alone could not alleviate the memory deficits in chronically stressed subjects. Therefore, exercise with both doses of escitalopram seems to have had additive effects on chronic stress conditions.

People mainly have a major interest in eating some palatable foods such as chocolate and sweet foods that influence brain functions. This study investigated the effects of acute, sub-chronic and chronic chocolate consumption with different percent of cocoa/sugar on learning, memory, memory consolidation and electroencephalogram (EEG) waves in rats.

Thirty-five male Wistar rats were allocated to five main groups containing control and sucrose as well as dark, milk and white chocolate groups. All groups were freely fed with chow, different kinds of chocolate and sucrose separately for 1,7 and 14 days as acute, sub-chronic and chronic food consumption. Also, memory and memory consolidation were evaluated using a passive avoidance test on days 1,7 and 14. In addition, brain electrical activity was evaluated by EEG.

Acute and sub-chronic dark and milk chocolate consumption significantly improved latency after day 1 and particularly day 7. In addition, only the chronic dark chocolate diet showed a significant enhancement in latency after 14 days. White chocolate and sucrose diets did not have significant effects on three latencies. The milk and dark chocolate diets changed nearly all brain waves of EEG, while the sucrose diet did not affect any of them.

Unlike sucrose and white chocolate, dark chocolate (acute, sub-chronic and chronic consumption) and milk chocolates (acute and sub-chronic consumption) had beneficial effects on memory and nearly all electrical brain activity probably due to high levels of cocoa and perhaps its antioxidant effect. Hence, these types of diets modified brain homeostasis and increased conscious state and relaxation reduction.

Depression impairs brain functions and memory processes. In a state of depression, escitalopram (as an antidepressant drug) and exercise (as an alternative lifestyle) both affect brain functions. Therefore, this study compared the therapeutic effects of exercise, using escitalopram at two different doses and exercise-accompanied escitalopram on different aspects of brain functions in rats with depression.

Male rats were randomly allocated into nine different groups of control, sham, depression, depression-rest, depression-exercise, depression-escitalopram 10, depressionescitalopram 20, depression-escitalopram 10-exercise and depression-escitalopram 20-exercise. Chronic restraint stress (6h/day, 14 days) was applied to induce depression. The escitalopram injections and treadmill running (1h/day, 14 days) were performed after the stress-induced depression. Moreover, different aspects of brain functions like learning, memory, memory consolidation and locomotor activity were evaluated via the passive avoidance test.

The results indicated that depression disrupted learning, memory and memory consolidation. Escitalopram at a dose of 20mg/kg, exercise-accompanied escitalopram 20mg/ kg and only exercise improved them significantly. In rats with depression, escitalopram at a dose of 10mg/kg (with and without exercise) enhanced memory in depression non-significantly. Moreover, the locomotor activity was decreased in groups with exercise-accompanied escitalopram 20mg/kg and exercise compared to only allowing a rest period after depression.

Overall, escitalopram 20mg/kg, exercise-accompanied escitalopram 20mg/kg and only exercise had therapeutic effects on memory improvement in subjects with depression. Since the combination of escitalopram 20mg/kg and exercise had a partial additive effect, it was the best treatment protocol for reversing the memory deficits in rats with depression.

Tramadol is an opioid analgesic with monoamine reuptake inhibitory effects. Although tramadol has been widely used to control pain, there is controversy about the risk of abuse. Therefore, in the present study, the acute effects of tramadol on neuronal activity in the medial prefrontal cortex (mPFC), which is one of the important centers of the reward system, were investigated electrophysiologically.

Tramadol was injected interperitoneally (12.5 and 25 mk/kg) or subcutaneously (40 mg/kg) and its effect on the firing of mPFC neurons was investigated, using in vivo extracellular single unit recording.

Tramadol could not significantly affect neural activity in mPFC, suggesting no acute and rapid effect on mPFC.

The present results showed that neural activity in mPFC was not rapidly affected by acute application of tramadol. Since the role of mPFC in tramadol addiction has been elucidated, it can be concluded that these effects may be due to delayed responses or chronic use of tramadol.

CA1, as a major structure involved in learning and memory, has been shown to be affected by tramadol addiction. Both orexin and endocannabinoid receptors express in CA1 and play an important role in drug dependency. The aim of this study was to evaluate the modulatory effects of orexin‑2 (OX2R) and endocannabinoid‑1 (CB1R) receptors on neuronal activity in CA1, in response to tramadol in rats.

Male Wistar rats were divided into 8 groups (n = 6–7); saline‑dimethyl sulfoxide (DMSO), tramadol‑DMSO, saline‑TCS‑OX2‑29, saline‑AM251, tramadol‑TCS‑OX2‑29, tramadol‑AM251, saline‑TCS‑OX2‑29‑AM251, tramadol‑TCS‑OX2‑29‑AM251. Tramadol was injected intraperitoneally, and then, AM251 (1 nmol/0.3 μL), CB1R antagonist and TCS‑OX2‑29 (1 nmol/0.3 μL), OX2R antagonist, were microinjected individually or concurrently into the CA1. Using in vivo extracellular single‑unit recording, the firing of CA1 pyramidal neurons was investigated.

Tramadol decreased neuronal activity in CA1 (P < 0.01) but increased it after micro‑injection of DMSO. TCS‑OX2‑29 increased neuronal activity in saline group (P < 0.05) but decreased it in tramadol group. AM251 had no effect on saline group but decreased neuronal activity in tramadol group (P < 0.05). Concurrent micro‑injection of TCS‑OX2‑29 and AM251 had no effect on saline group but decreased neuronal activity in tramadol group (P < 0.05).

Our findings suggest that neural activity in CA1 is rapidly affected by acute use of tramadol, and some of these effects may be induced through the endocannabinoid and orexin systems. Thus, the function of endocannabinoid and orexin systems in CA1 may play a role in tramadol addiction.

In the present study, the effects of intra‑basolateral amygdala (BLA) blockade of dopamine D1 receptor on morphine‑induced conditioned place preference (CPP) were investigated in male Wistar rats.

A 5‑day CPP paradigm was used. Morphine was injected subsequently at effective (5 mg/kg) and ineffective (0.5 mg/kg) doses. SCH 23390 (0.5– µg/rat), as a selective D1 receptor antagonist, was microinjected bilaterally into the BLA.

Effective dose of morphine induced a significant CPP, and increased the locomotor activity during the testing phase. The results showed that morphine‑induced CPP was significantly suppressed by D1 receptors antagonist in BLA in the acquisition phase and caused an aversion even at high doses. The antagonist also significantly prevented CPP expression. Morphine increased the motor activity, but the D1 receptors blockade, significantly reduced it.

The findings of this study suggest a possible role for BLA dopamine D1 receptors in reward responses in morphine dependency.

 Different nutrients affect brain functions. This research investigated the effects of acute, sub-chronic, and chronic consumption of sucrose and different kinds of chocolate (with various cocoa and carbohydrate percentage) as portable nutrients on anxiety, locomotor activity, food consumption, and body weight differences (BWD) in male rats.

 Thirty-five male Wistar rats (200-250 g) were divided into five experimental groups: standard food (control), dark chocolate, milk chocolate, white chocolate, and sucrose for 14 days. Anxiety and locomotor activities were evaluated on days 1,7, and 14 using open field test (OFT). Then, food consumption and BWD were measured.

 The sub-chronic consumption of sucrose and white chocolate significantly decreased total crossing number of OFT compared to control group. Moreover, acute consumption of sucrose tended to significant decreases in central crossing number. The sub-chronic dark chocolate consumption showed a significant enhancement of central crossing number. In different mono-diet of nutrients, the food consumption showed significant decreases in all groups compared to control group. The BWD had significant decreases in the first seven days. In addition, The BWD showed significant decreases in sucrose, milk chocolate, and dark chocolate during the final seven days.

 Anxiety significantly decreased by sub-chronic consumption of dark chocolate and acute sucrose consumption. Moreover, sub-chronic sucrose and white chocolate consumption decreased locomotor activity in subjects. While, regardless of nutrient types, the mono-diet could cause major weight loss. Further weight loss occurred with a high concentration of cocoa in the dark chocolate mono-diet.

Chronic stress, which has been prevalent in human life, induce structural changes in the hippocampus. Depression and impairment of memory are serious comorbidities of chronic stress. In this study, we evaluated the impact of an Iranian honey pretreatment on memory deficit, depression and the hippocampal neuronal loss in the chronic unpredictable mild stress (CUMS) model.

Adult male Wistar rats were divided into the control groups that received water or honey (0.2 or 2g/kg) and CUMS groups that subjected different, randomly and unpredictable mild stressors for 4 weeks. Ten days before starting the CUMS procedures, the animals received honey (0.2 or 2g/kg, daily, orally), which was continued until sacrificing. Morris water maze and sucrose performance tests were used to evaluate the spatial learning and memory and depressive-like behavior in the animals respectively. Hippocampus and whole brain samples were collected for further biochemical and histological analysis.

Honey reversed the depression-like behavior and ameliorated the spatial memory deficit induced by CUMS. Also, honey decreased cell death in the hippocampus and reduced the malondialdehyde level in treated animals.

These results revealed that honey diminished learning and memory deficits and depression in chronic stress conditions.

Studies have shown that exercise can affect learning and memory. This study intended to investigate the effect of short-term aerobic exercise on memory and learning in both behavioral and electrophysiological methods.

In this research, 30 male Wistar rats were divided into two groups of 10 for electrophysiological testing, and 2 groups of 5 for behavioral testing. First, the exercise groups were compelled by a running wheel machine at 17.5 m/minute for 2 hours per day, during 10 days. Then, in both exercise and control groups, using electrophysiological method, long-term potentiation was induced and synaptic plasticity change in the CA1 region was recorded and evaluated for 90 minutes. Exercise and control groups were trained in passive avoidance device to evaluate the effect of exercise on memory recall, and were tested at 0 and 24 hours, and one week after receiving shocks.

In the electrophysiological method, the index of recorded responses (field excitatory postsynaptic potentials) was not significantly different between exercise and control groups. In the passive avoidance learning test, the delay time of entering the dark room at 0 and 24 hours and one week after receiving shocks in the control group was significantly longer than the exercise group, and the time of staying in the dark room in exercise group was significantly longer than control group, 24 hours after receiving the shock.

It can be concluded that short-term moderate intensity exercise cannot significantly change the avoidance memory and cognitive activity of the animal, and will not affect changes in synaptic plasticity in the animal.

The nucleus accumbens (NAc) express both orexin-2 receptor (OX2R) and cannabinoid receptor type 1 (CB1R). Orexin and cannabinoid regulate the addictive properties of nicotine. In this study, the effect of the CB1R blockade on the electrical activity of NAc neurons in response to nicotine, and its probable interaction with the OX2R in this event, within this area, were examined via</em> the single-unit recording.

Experimental approach: 

</em>The spontaneous firing rate of NAc was initially recorded for 15 min, and then 5 min before subcutaneous injection of nicotine (0.5 mg/kg)/saline, AM251 and TCS-OX2-29 were injected into the NAc. Neuronal responses were recorded for 70 min, after nicotine administration.

Nicotine excited the NAc neurons significantly and intra-NAc microinjection of AM251 (25 and 125 ng/rat), as a selective CB1R antagonist, prevented the nicotine-induced increases of NAc neuronal responses. Moreover, microinjection of AM251 (125 ng/rat), before saline injection, could not affect the percentage of change of the neuronal response. Finally, simultaneous intra-NAc administration of the effective or ineffective doses of AM251 and TCS-OX2-29 (a selective antagonist of OX2R) prevented the nicotine-induced increases of NAc neuronal responses, so that there was a significant difference between the group received ineffective doses of both antagonists and the AM251 ineffective dose.

The results suggest that the CB1R can modulate the NAc reaction to the nicotine, and it can be concluded that there is a potential interplay between the OX2R and CB1R in the NAc, in relation to nicotine.

Inflammation is one of the effective factors, in the development of functional disorders of the nervous system. Pentoxifylline (PTX) has an inhibitory effect on inflammatory factors. Therefore the aim of this study was to evaluate the effect of PTX on learning, memory and expression of genes, involved in neuronal survival in the rat hippocampus, following systemic lipopolysaccharide (LPS) injection.

Male rats were randomly divided into 5 groups of control, LPS and LPS + PTX, receiving doses of 10, 25 and 50 mg/kg of PTX, respectively. In LPS groups, LPS was injected (5 mg/kg; intraperitoneal), and after one week, rats received intraperitoneal PTX for 14 days, in the treatment groups. Learning and memory were evaluated by object location task (OLT) and novel object recognition (NOR). Then, the hippocampus was dissected in order to measure the expression of the associated genes.

The results showed that peripheral LPS injection caused significant damage (P < 0.01) to learning and memory with respect to controls, but PTX with doses of 10 and 50 mg/kg prevented these impairments. Results from reverse transcription polymerase chain reaction (RT‑PCR) showed that LPS significantly increased the expression of Bax and TNF‑ with respect to controls. PTX in the LPS + PTX group significantly increased the expression of Bcl‑2, BAD and Caspase‑3.

Other than the increased Bcl‑2 expression, PTX had no significant effect on the expression of other genes, therefore further studies are needed to find out how PTX improves the learning and memory impairments, following the peripheral inflammation.

Stress influences cognitive behavior adversely, whereas dark chocolate exhibits positive effects on memory processes. This study investigated the effects of different dark chocolate diets on various aspects of brain functions in rats under chronic stress

Thirty-five rats were randomly allocated into five groups: control, stress, stress with different (compulsory, optional and restricted) dark chocolate diets. Latency, dark stay (DS) time and the number of entrance to the dark compartment were respectively evaluated as memory, memory consolidation and locomotor activity by passive avoidance test.

There were significant differences between initial latency and latency after 1 day in all groups. In the stress-compulsory and restricted dark chocolate diet groups, latency after 1 day increased significantly. Moreover, the DS time was not significantly higher in the stressed group than the control group. The DS time and number of entrance to dark compartment decreased significantly in the stress-compulsory dark chocolate diet group compared to the stressed group. Furthermore, the number of entrance to dark compartment was significantly higher for the stress- optional dark chocolate diet compared to those with the compulsory diet. Additionally, serum and hippocampal corticosterone levels, except in the frontal cortex, were significantly lower only in the stress-compulsory dark chocolate diet group compared to the stressed group.

Different dark chocolate diets had various effects on brain functions under chronic stress. Respectively, the compulsory and optional dark chocolate diets had the best and least effects on brain function improvement. Only the compulsory dark chocolate diet could improve brain functions such as memory, memory consolidation and locomotor activity.

Peripheral inflammation is effective in the development of neurodegenerative diseases. Pentoxifylline (PTX) has an inhibitory effect on inflammatory cytokines; therefore, we aimed to evaluate the effect of PTX on passive avoidance learning and the expression of tumor necrosis factor-alpha (TNF-α) and caspase-3 in the rat hippocampus, following systemic lipopolysaccharide (LPS) injection.

Male Wistar rats were randomly divided into five groups: control, LPS, and LPS + PTX, receiving doses of 10, 25, and 50 mg/kg of PTX, respectively. The animals received daily injections of PTX (i.p.) 1 week before and 2 weeks after the LPS injection (5 mg/kg; i.p.). Learning and memory were evaluated by passive avoidance learning. Then, the expression of the associated genes was measured in the hippocampus.

The results showed that the peripheral LPS injection had no significant effect on learning and memory. PTX only with a dose of 10 mg/kg shows an improvement (P < 0.05). Results from reverse transcription polymerase chain reaction showed that LPS had no significant effect on the expression of caspase-3 and TNF-α. PTX with a dose of 10 mg/kg decreased the caspase-3 expression in the LPS + PTX group (P < 0.001), but the expression of both genes increased, using other concentrations.

Findings showed that systemic application of LPS after 2 weeks had no effect on learning and memory and the expression of inflammatory genes in the hippocampus, but PTX led to an increase in the expression of these genes, which could be due to its direct effects or possible exacerbation of LPS effects.

Spathe of phoenix dactylifera is hard-covering envelope of date palm which is mentioned as a nerve relief in ancient medicine books. In this experiment, three extract doses used in sleeping time, sedative efficacy, and electroencephalography (EEG) protocol to show different aspects of extract effects on sleep.

In three sleeping time, anesthesia time and EEG experiment protocols test group containing three extract doses (62.5, 125, and 250 mg/kg) were compared with saline control group, and in sleeping time experiment control group contained intact, midazolam, and saline group to detail more in behavioral Angel method.

Three extract doses increased sleeping time when compared with saline control group (P < 0.05). In evaluated sedative efficacy, two 125 and 250 mg/kg doses increased anesthesia and showed sedative effect (P < 0.05). In EEG experiment, dose 125 mg/kg increased delta waves and decreased high-frequency waves of alpha and beta. In addition, there were significant decreases in alpha waves of 62.5 and 250 mg/kg doses.

Although all three doses increased sleeping time, dose 125 mg/kg is more efficient for deep and relaxing sleep and suits more for related researches.

The aim of this study was to evaluate the effects of acute kidney injury (AKI) and mediatory role of the estrogen on passive avoidance memory in ovariectomized rats. Frothy ovariectomized Wistar rats were subjected to sham-vehicle, sham-estrogen, renal ischemia reperfusion (RIR)-vehicle, and RIR-estrogen groups. AKI was induced by ischemia reperfusion. Estrogen (200 μg/kg in 0.2 ml/100 g body weight) was injected subcutaneously once a week for four weeks. Then, passive avoidance memory was assessed. AKI resulted a significant decrease in the mean latency of entering the dark chamber (P < 0.010). Although, estrogen therapy following AKI led to elevated blood urea nitrogen (BUN) and creatinine, but, there was no significant difference in the delay in entering the dark chamber in RIR-estrogen group compared to RIR-vehicle group (P = 0.100). The results showed that AKI could have a deleterious effect on passive avoidance memory. However, the studied dose of estrogen cannot prevent passive avoidance memory impairment induced by AKI.

Many studies have focused on ventral tegmental area than of other mesocorticolimbic areas, and implicated a key role for the medial prefrontal cortex (mPFC) in the development of addictive behaviors. So far, the role of gamma-aminobutyric acid (GABA) receptors in the discriminative properties of morphine has received little attention and few studies evaluated the role of these receptors in drug dependence. Hence, we investigated the role of this receptor on morphine- induced GABA/ glutamate (GLU) changes in the mPFC following morphine administration using in vivo microdialysis. In this study, 60 rats weighing 270-300 g were divided into six groups. First, microdialysis probe was inserted into the mPFC and was perfused with artificial cerebrospinal fluid and collected the baseline samples in all groups. In saline and morphine groups, the saline, in phaclophen and (phaclofen+morphine) groups, phaclofen (100 nmol), and in bicuculline and (bicuculline+morphine) groups, bicuculline (20 nmol) was injected intracerebroventricular. In saline, phaclofen and bicuculline groups 20 min later, animals received saline (0.2 ml, IP) and others groups received morphine (20 mg/kg, IP). Our results showed that morphine increased the average concentration of GABA and decreased the concentration of GLU within mPFC. Pretreatment with phaclofen and bicuculline 20 min before morphine administration had no effect on GABA and GLU release for 100 min. The present study indicated that morphine influence the GABA and GLU transmission in mPFC. Therefore evaluation of neurochemistry changes of this neural circuitry may provide further insight into the mechanisms underlying drug dependence.

Stress affects brain functions and induces psychological disorders. Previous studies have indicated different effects of crocin and exercise on the improvement of memory in some types of stress. The present study investigated the effect of crocin, exercise, and crocin‑accompanied exercise on learning, memory, and memory consolidation in rats under chronic unpredictable stress (CUS).

Male rats were randomly allocated to different groups: control, sham, stress, stress‑exercise, stress‑crocin, and stress‑crocin‑accompanied exercise groups. The CUS and treadmill running were applied 2 h/day and 1 h/day, respectively, for 21 days. Crocin (30 mg/kg) was daily intraperitoneally injected to the rats and their behavioral variables were evaluated as a brain function using the passive avoidance test.

Results showed that the CUS significantly decreased learning and memory compared to the control group, while crocin alone and crocin‑accompanied exercise significantly improved learning and memory compared to the stressed group. It was found that exercise alone caused learning but did not improve memory in unpredictable stress rats.

The data indicated that unpredictable stress had very destructive effects on the brain functions. Furthermore, unlike exercise, crocin improved memory under unpredictable stress conditions. Overall, it seems that the beneficial effects of crocin‑accompanied exercise on learning and memory were probably because of crocin, but not exercise.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system which has no any known defnitive treatment. Studies have shown that thyroid hormones (THs) in addition to their roles in the development of the nervous system and the production of myelin have important roles in the adult’s brain function. Since the only way to treat MS is the restoration of myelin, the aim of this study was to evaluate the effects of levothyroxine on visual evoked potential (VEP) impairment following local injections of lysolecithin into the rat optic chiasm.
To induce demyelination, lysolecithin was injected into the optic chiasm of male Wistar rats. VEP recording was used to evaluate demyelination and remyelination before and 10, 17, and 24 days after the
lysolecithin injection. The rats received an intraperitoneal injection of levothyroxine with doses 20, 50, and 100 μg/kg in different experimental groups.
VEP latency and amplitude showed demyelination at 10 and 17 days after an induced lesion in MS group which was reversed at day 24. Levothyroxine prevented these impairments, especially in high doses.
According to the results, lysolecithin‑induced demyelination at optic chiasm and VEP impairments can be restored by administration of levothyroxine. Therefore, THs probably have positive effects in demyelinating diseases.

Alzheimer's disease is a disorder associated with neuronal degeneration in the areas involve in learning and memory. It has been proposed that erythropoietin probably has neuroprotective effects. Therefore, the aim of the present study was to evaluate the effect of erythropoietin on neuronal apoptosis in the granular layer of dentate gyrus of the hippocampus in an animal model of Alzheimer's disease.
Animal model of Alzheimer's was established via bilateral intracerebroventricular (ICV) injection of streptozotocin (STZ). After 2 weeks and observation of cognitive disorder, rats received intraperitoneal (IP) injection of erythropoietin every other day with a dose of 5000 IU/kg for 2 weeks. Finally, the rats were anesthetized and their brains were dissected for immunohistochemical study. Terminal deoxynucleotidyl transferase biotin-dUTP Nick-End Labeling (TUNEL) method was used to study neuronal apoptosis.
Findings: Intracerebroventricular injection of streptozotocin increased the number of apoptotic cells in the granular layer of dentate gyrus significantly (P The results of this study indicate that erythropoietin may be effective in reducing the complications of neurodegenerative diseases by reducing neuronal apoptosis.

There is an increase in inflammatory and a reduction in anti‑inflammatory cytokines in multiple sclerosis (MS). Considering the role of thyroid hormones in the development and regulation of both neural and immune systems, the aim of this study was to evaluate the effects of levothyroxine on serum concentrations of interleukin‑10 (IL‑10) and interferon gamma (IFN‑γ) in animal models of MS.

To induce demyelination in male Wistar rats, lysolecithin was injected into the optic chiasm. Then levothyroxine was injected intraperitoneally (20, 50, and 100 µg/kg) for 21 days. Serum levels of cytokines were measured by enzyme‑linked immunosorbent assay at 7, 14, and 21 days after that.

The results showed that injection of lysolecithin to the optic chiasm only increased serum concentrations of IL‑10 compared to the sham group (P < 0.05) at 7th day, but this increase was prevented by all doses of levothyroxine. IFN‑γ was decreased significantly (P < 0.001) 21 days after. Comparing to the sham group at all sampling time and with respect to the MS group at the days 7 and 21, levothyroxine decreased serum concentrations of IFN‑γ significantly.

The results showed that thyroid hormones probably could produce protective effects against induced demyelination through affecting immune responses.

Cholecystokinin (CCK) has been proposed as a mediator in stress. However, it is still not fully documented what are its effects. We aimed to evaluate the effects of systemic administration of CCK exactly before induction of stress on spatial memory and synaptic plasticity at CA1 in rats.
Male Wistar rats were divided into 4 groups: the control, the control-CCK, the stress and the stress-CCK. Restraint stress was induced 6 hr per day, for 24 days. Cholecystokinin sulfated octapeptide (CCK-8S) was injected (1.6 µg/kg, IP) before each session of stress induction. Spatial memory was evaluated by Morris water maze test. Long term potentiation (LTP) in Schaffer collateral-CA1 synapses was assessed (by 100 Hz tetanization) in order to investigate synaptic plasticity.
Stress impaired spatial memory significantly (P The present results suggest that high levels of CCK-8S during induction of stress can modulate the destructive effects of stress on hippocampal synaptic plasticity and memory. Therefore, the mediatory effects of CCK in stress are likely as compensatory responses.

Studies have shown that pentoxifylline (PTX) in addition to protective effects on blood vessels probably has positive influence against the brain inflammation. Therefore, the aim of this study was to evaluate the effects of PTX on serum levels of interleukin 10 (IL‑10) and interferon gamma (IFN‑γ) and passive avoidance learning in lipopolysaccharide (LPS)‑induced inflammation in rats.

Inflammation was induced by intraperitoneal (i.p.) injection of LPS (0.5 and 5 mg/kg) in male Wistar rats. After a week, PTX (25 mg/kg; i.p.) was injected for 14 days. Passive avoidance learning test was used for evaluation of learning and memory. Serum levels of cytokines were measured by enzyme‑linked immunosorbent assay.

The behavioral results did not show any significant effect of LPS and PTX on learning and memory. Both doses of LPS (0.5 and 5 mg/kg) decreased IL‑10 significantly (P < 0.05). PTX prevented this reduction just in the LPS 0.5 mg/kg + PTX 25 mg/ kg group. Serum level of IFN‑γ was increased only in the LPS 0.5 mg/kg + PTX 25 mg/kg group comparing to the LPS 0.5 mg/kg group (P < 0.05).

The results showed that LPSinduced inflammation decreased the serum levels of IL-10. PTX could prevent these decreases only in mild inflammation. Both PTX and LPS-induced inflammation had no significant effects on learning and memory; therefore, their effects on CNS require further study.