مجله فیزیولوژی و فارماکولوژی ایران
سال ششم شماره 1 (پیاپی 16، بهار و تابستان 1401)

Cardiovascular diseases are among the main causes of mortality in the elderly. Signaling of mitochondrial biogenesis has a crucial role in cardiovascular energy homeostasis. The purpose of this study was to compare the effect of high and moderate intensity resistance training on the myocardial gene expression of some mitochondrial signaling molecules including AMPK, PGC-1α, TFAM and cytochrome C in the elderly rats.

Twenty-five male Wistar rats with 23 months old and 437 g average weight were randomly assigned to control (n = 8), resistance training (RT) with high intensity [HRT, 80% of maximum voluntary carrying capacity] (n = 8), and moderate intensity [MRT, 60% of maximum voluntary carrying capacity] (n = 9). RT included 5 days/week of climbing a ladder for 8 weeks. Seventy-two hours after the last training session, myocardial gene expression of AMPK, PGC-1α, TFAM and cytochrome C were measured by Real Time Polymerase Chain Reaction. One-way analysis of variance and Tukey post-hoc test were used for statistical analyses and p <0.05 was considered the significant level.

PGC-1α gene expression significantly increased in both HRT and MRT groups compared to the control group (p < 0.05). MRT significant increased  cytochrome C gene expression, compared to the control group (p < 0.05).

In elderly rats, HRT and MRT can improve PGC-1α myocardial expression, wheras MRT improves the cytochrome C myocardial expression. These effects can be useful in improving the energy homeostasis of myocardial cells in the elderly.
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Cognitive functions and hydrogen sulfide (H2S) metabolism are impaired by high fat diet (HFD). Therefore, the aim of this study was to examine the potential effect of sodium hydrosulfide (NaHS) (as H2S donor) on spatial learning and memory in male rats fed with HFD.

After 11 weeks of normal and HFD diet with and without NaHS treatment (at doses of 3 and 5 mg/kg) in male rats, Barnes maze was used to assess memory and spatial learning.

During training days there were not significant differences in escape latency, traveled distance and the number of errors in finding the escape box between experimental groups. HFD and control + NaHS (5 mg) groups made significantly more errors on the test day (probe trial) than control rats. Also, the number of errors in the HFD animals with NaHS (5 mg) decreased compared to the HFD group alone.

Based on our observation, HFD has no significant effect on the acquisition of Barnes test but causes impaired memory retrieval. In addition, administration of NaHS reverses HFD-induced memory impairment. In control animals, the administration of NaHS increased the number of errors in the probe test, which may indicate the presence of memory deficits.
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There are numerous reports that different models of stress can cause memory loss. On the other hand, investigations determined that Cyperus rotundus rhizome can effectively improve memory and enhance recall. In the present study we assessed the possible improving effects of hydroalcoholic extract of Cyperus rotundus rhizomes on stress-induced memory retrieval impairment.

Adult male mice were divided to two  main groups, stress and non-stress, and each of these groups was divided into two subgroups: saline-receiving control and treated with Cyperus rutundus extract. First, the mice received the material by daily gavage for 7 or 21 days. One day after the last gavage, the animals were trained by step-through method. 24 hours after the training, they were exposed to elevated platform stress before the test. Step-through latency (STL) to enter dark chamber and spent time in dark chamber (STD) were recorded as measures of passive avoidance memory retrieval.

Pre-test stress significantly reduced STL and increased STD. Pre-training gavage of Cyperus rotundus extract reversed the STL and also significantly reduced the STD.

It seems that treatment with hydroalcoholic extract of Cyperus rotundus rhizomes improves ability to retrieve information from long-term memory and  ameliorates stress-induced memory impairment in a time-dependent manner.
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In recent years, many studies have suggested the essential role of the prolyl isomerase Pin1 enzyme in protecting against age-related neurodegeneration in Alzheimer's disease (AD). This enzyme is involved in the conformational changes of the two key proteins including amyloid precursor proteins (APP) and tau protein from dysfunctional (cis) to properly functional (trans) form. Promoting non-amyloidogenic degradation of APP, restoring tau function in microtubule assembly, and inducing tau dephosphorylation are among the main results of the Pin1 physiological functions. In AD, the lack of Pin1 activity slows down the rate of isomerization, which promotes the amyloidogenic pathway and induces the formation of neurofibrillary tangles (NFTs). The exact molecular mechanisms of Pin1 dysregulation in AD have not yet been elucidated. However, the findings suggest that Pin1 may be a new target in managing AD at early stages, and investigating the regulation of its expression in neurons could help achieve this goal.

Hypertension-induced left ventricular hypertrophy is an independent risk factor of heart failure and sudden death. Progression of cardiac hypertrophy is accompanied by activation of apoptosis signaling pathways. Tropisteron is a 5HT-3 receptor antagonist that its cardioprotective effects has been revealed by recent studies. Though, the underlying mechanisms are still unclear. The aim of the current study is to investigate the effect of tropisetron on gene expression of BNP (as the hypertrophy marker) and pro-apoptotic factors (BAD and BAX) in the rat model of hypertrophic heart.

Male Wistar rats (n = 24) were divided to the following groups: (I) control group including intact animals, (II) un-treated hypertrophy group (hypertrophy), (III) tropisetron-treated rats (3 mg/kg/day, 21 days)  during progression of hypertrophy (tropisetron + hypertrophy group), (IV) tropisetron-treated rats without induction of hypertrophy (tropisetron group). The left ventricular hypertrophy model was induced by surgical abdominal aortic banding. Gene expression was assessed by Real-time PCR.

cardiac BNP mRNA level increased significantly in Hypertrophy group compared to the control (p < 0.001). In the tropisetron + hypertrophy group, BNP mRNA level was decreased significantly when compared with un-treated Hypertrophy group (p < 0.05). The transcription level of BAD was also upregulated in left ventricle of un-treated hypertrophy group (p < 0.001 vs. control). However, in the Tropisetron+Hypertrophy group, BAD mRNA level was decreased significantly compared to the untreated hypertrophy group (p < 0.001). The transcription level of BAX did not change significantly among the experimental groups.

Tropisetron can prevent the progression of pressure overload-induced hypertrophy to heart failure at least in part by decreasing BAD expression.
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Feeding behavior is regulated via a complex network which interacts via diverse signals from central and peripheral tissues. The present study was designed to examine the interaction between glutamatergic and dopaminergic systems on food intake in neonatal meat chicken.

In this study, 264 day-old chicken (ROS 308) were used. In each experiment, chickens divided to 4 experiments including 1 control and 3 treatment groups (n = 11). In experiment 1, chicks ICV injected with normal saline, 6-OHDA (neurotoxin, 2.5 nmol), kainic acid (ionotropic glutamate receptors agonist, 300 nmol) and 6-OHDA + kainic acid. Experiments 2-3 were similar to experiment 1, except injections of the SHC23390 (D1 receptors antagonist, 5 nmol) and AMI-193 (D2 receptors antagonist, 5 nmol) were done instead of 6-OHDA. In experiment 4, saline, 6-OHDA (2.5 nmol), trans-(±)-ACPD monohydrate (metabotropic glutamate receptor agonist, 300 nmol) and co-injection of the 6-OHDA+ trans-(±)-ACPD monohydrate were done. Experiments 5 and 6 were similar to experiment 4, except SHC23390 and AMI-193  were injected instead of 6-OHDA. Then the cumulative food intake measured until 120 min post injection.

Kainic acid significantly decreased food intake (p ≤ 0.05). 6-OHDA and SHC23390 decreased kainic acid and trans-(±)-ACPD- induced hypophagia (p ≤ 0.05).

Interaction between dopaminergic and glutamatergic systems mediates via ionotropic and metabotropic glutamate and D1 dopamine receptors.
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One of the most effective factors in control of attention is the amount of reward associated with the target stimulus. The aim of this study was to investigate effects of different reward magnitudes on saccadic eye movement parameters as a behavioral index of attention.

We used two male macaque monkeys in a saccadic behavioral task. Monkeys trained to saccade to a presented stimulus that was associated with low, medium, or high reward magnitudes. For two monleys, latency, peak velocity and accuracy of saccades in two separate groups (fast and slow) in three reward regimes were analyzed using three ways ANOVA and Bonferroni post-hoc tests.

Latency of the saccades to stimuli associated with higher reward magnitude was lower compared to latency of saccades to the stimuli associated with smaller reward magnitudes. The saccades were more accurate when targeting stimuli associated with higher reward magnitudes than targeting low reward stimuli. Changes in the reward associated with the saccadic targets did not consistently affect the saccadic peak velocity.

The reward associated with saccadic target stimuli resulted in a decrease in saccadic reaction times and improvement in accuracy of saccades, with inconsistent effects on saccade velocity. Our observations are consistent with current literature showing value as a main component in guiding attention.
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Spinal cord injury (SCI) is a debilitating sensory-motor dysfunction. Neuropathic pain and motor dysfunction are the most common types of dysfunctionality after SCI, which reduces the quality of life. So far, SCI treatment has not been completely effective and researchers are seeking for novel alternative/potent therapies. Metformin has shown antioxidant and anti-inflammatory effects on the central and peripheral nervous systems. In the present study, the probable neuroprotective and antioxidant effects of intrathecal metformin administration was evaluated on the neuropathic pain and motor dysfunction after SCI.

Thirty-five rats were divided into five groups: sham, SCI, and metformin (Met) at doses of 1, 2 and 4 mM. Hot plate, acetone, and von Frey behavioral tests and weight changes were performed on days 7, 14, 21, and 28 after SCI. The changes in serum levels of catalase and glutathione, as well as nitrite level, and numbers of sensory and motor neurons were measured on day 28 after surgery.

Intrathecal injection of metformin reduced heat, cold and mechanical pain, motor activity, and modulated weight changes in rats after SCI. Intrathecal metformin also attenuated serum changes of catalase and glutathione, decreased serum nitrite, and increased survived sensory and motor neurons after SCI.

Employing the neuroprotective and antioxidant potential of intrathecal metformin administration could reduce neuropathic pain and improve motor dysfunction following SCI.
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Traumatic brain injury (TBI) is a global health problem. Persian medical manuscripts recommended phlebotomy as a potent treatment for TBI. This study aimed to evaluate the possible effect of saphenous vein phlebotomy (SVP) on neuroinflammation after TBI.

Adult male Wistar rats were divided randomly into three main groups (n = 12): sham group, TBI group, and TBI+SVP group. Induction of trauma was made through a controlled cortical impactor (CCI) device and SVP treatment was applied 10 min after TBI. Then, neurological functions were evaluated 6 and 24 hours post-surgery. Furthermore, 6 hours after bloodletting inflammatory and oxidative stress biomarkers were measured in the rats' brains.

Therapeutic phlebotomy could improve neurological scores post-TBI. In addition, phlebotomy application significantly reduced proinflammatory cytokines (IL- 1β, IL-17, and TNF-α) and oxidative stress factors as shown by reduction of malondialdehyde (MDA) and elevation of superoxide dismutase (SOD) with no significant effect on glutathione peroxidase (GPx) and nitric oxide (NO) in the brain 6 h after TBI.

Finally, SVP possibly through its attenuation of neuroinflammation and free radicals, and also increased antioxidant activity in the rats' brains could ameliorate neurological impairment following TBI.

Drug addiction is a serious medical and social problem around the world. More than 50 percent of substance use cases were initiated between the ages of 15-19. Adolescence is the period between childhood and adulthood. In rats, the period between postnatal days (PND) 28 and 42 is considered the early-mid adolescence (12–17 years in human), whereas the later interval (PND 43–55) may model the late adolescence/emerging adulthood period (18–25 years in humans). Adolescence is a critical time of brain development and maturation. Many researchers have shown that certain epigenetic changes can transfer from parents to offspring through DNA methylation, histone acetylation and different types of small noncoding regulatory RNAs. There is compelling evidence for the effect of parental drug abuse such as opioid, cocaine, nicotine, cannabinoid and alcohol on the offspring. In this report, we will study the effects of Adolescent drug abuse on behavior and cognitive aspects of offspring.

Glioblastoma multiform is one of the most common primary malignant brain tumors in adults. Recent studies have shown that micronutrients, such as selenium, have the potential to have positive effects in the treatment of glioblastoma and can be a promising candidate combined with surgical and radiochemical therapies. The aim of this study was to evaluate the anti-cancer effects of selenium on brain tumor damages.

Rats were randomly divided into three main groups: control and selenium-received groups at doses of 0.5 and 1.5 mg/kg. A 1 × 106 rat Glioma C6 cells were transplanted in the right caudate nucleus of the rat brain. Five days after surgery, the treatment groups received selenium intraperitoneally for five days. Motor activity, animal weight, tumor volume, survival rate, and histopathological changes were assessed.

Selenium 0.5 mg/kg reduced tumor volume, improved locomotor activity, and attenuated weight loss of the animals. Also, histological analysis showed a significant reduction in tumor volume and invasion of tumor cells to the surrounding tissues of tumor in rats treated by selenium 0.5 mg/kg.

According to the present results, it can be stated that selenium has sufficient potential to inhibit brain tumor damages.

Menthol is a monoterpene and the main component of essential oils of mint plants family. The sedative and anxiolytic effects of this compound have been reported, previously. However, mechanism of its anxiolytic action has not been elucidated. In this study, the effects of systemic administration of menthol in the open field test and elevated plus maze, also the possible mechanism of its anxiolytic effect in the elevated plus maze were investigated.

In the first phase of this study, mice in 8 separate groups received doses of 5, 10, 20, 50 and 100 mg/kg of menthol, diazepam and buspirone 30 minutes before the behavioral tests to assess anxiety. Based on the results, 50 mg/kg was determined as the effective dose of menthol. In the second stage, flumazenil as a benzodiazepine receptor antagonist and WAY 100635 as a serotonin receptor antagonist were applied to determine the underlying mechanism involved in the anxiolytic effect of menthol.

The present study showed that menthol, especially at the dose of 50 mg/kg, significantly reduced the number of lines, trimming and rearing behavior in the open field test, and increased the number of entries into the open arm and the time spent in the open arm, in the elevated plus maze (p < 0.05). Flumazenil administration reversed these effects in the elevated plus maze, whereas WAY100635 had no effect on it.

Menthol exerts its anxiolytic effects in the mouse elevated plus maze through the benzodiazepine not serotonin pathway.

Adipokine apelin is involved in energy metabolism and the pathogenesis of diabetes. Apelin can have anti-type 2 diabetes activity and be effective in reducing insulin resistance as an insulin-sensitizing agent. Also, reviewing the effects of different types of exercise on apelin can answer many questions about exercise-induced apelin, and identify the therapeutic role of exercise on apelin and diabetes. Therefore, in the present review article, the effect of chronic and acute exercise on apelin in type 2 diabetes, and the mechanisms of the effect of exercise on apelin and insulin sensitivity are presented.

Few studies have evaluated the effect of acute exercise on apelin in type 2 diabetes, and most of the studies on the effect of chronic exercise have been of the aerobic type, with contradictory results (the increase and decrease of the apelin) reported. Also, it seems that exercise, independently of body weight changes by improving insulin sensitivity can affect adipose tissue and circulating apelin, and thus reduce insulin resistance in type 2 diabetes. Therefore, apelin and exercise as insulin-sensitizing agents can increase energy metabolism and improve insulin sensitivity by similar mechanisms.

Exercise-induced apelin can be a promising therapeutic strategy and target for type 2 diabetes. However, further studies are needed to determine how different types of exercise affect apelin, as well as the exact association of exercise-induced apelin with the pathogenesis of type 2 diabetes and related mechanisms.

Cortical cholinergic transmission is crucial for higher cognitive functions like attention, and cognitive impairments like Alzheimer’ disease coincides by abnormal cholinergic system.  Physiological and pharmacological observations suggest that acetylcholine at the thalami-cortical synapse mediates dynamic control of visual input to the cortex. In this study we investigated roles of nicotinic acetylcholine agonists on perceptual sensitivity in primary visual cortex in macaque monkeys.

Experiments performed on a male rhesus macaque (weighing 8-10 kg). After implanting a titanium head-holder, the animal trained in a detection task. First, we determined receptive location of the injection site by electrophysiological recordings. Then we injected nicotine using a microinjectrode system.

Nicotinic acetylcholine agonist, Nicotine, significantly increased detection threshold of visual stimuli.

Primary cortical nicotinic acetylcholine receptors are involved in modulating perceptual sensitivity in a detection task. Understanding roles of thalamocortical acetylcholine receptors is fundamental to understanding sensory perception in normal and cognition-impaired people.

Rabies is caused by the neurotropic rabies virus from the genus Lyssavirus belonging to the Rhabdoviridae family. Despite extensive neurological symptoms including anxiety, rage, hallucinations, depression and hydrophobia, mild pathological alterations are usually seen in the rabies-infected brain. Rabies virus encodes five proteins named N, L, P, M and G. Glycoprotein G forms spikes on the external surface and enables the virus to enter the host cells by connecting and fusing with the cell membrane. The C-terminus amino acid residue of glycoprotein G, called PBM (PDZ binding motif), determines the viral pathogenesity and may manipulate different signaling pathways in the infected neurons. Rabies virus glycoprotein G has been shown to facilitate both short-term and long-term synaptic plasticities, enhances hippocampal-dependent spatial memory performance, and triggers anxious behavior in the infected rats. In this paper, we will review how the rabies virus can alter synaptic function using its glycoprotein G and how it can be used for drug delivery to the central nervous system and for tracing neural networks.

Dementia is an age-related disease occurring in older people associated with symptoms like cognitive disorders, behavioral disturbance, and memory loss. The common types of dementia include Alzheimer's disease, vascular dementia, Lewy bodies’ disease, and frontotemporal dementia. With the growing body of medicine, there is still an unclear question about dementia pathology due to the multifactorial nature of dementia. One aspect is the damage to the brain white matter, which has attracted attention. Oligodendrocytes (OLs), the essential myelinating cells of the axons in the central nervous system, are one of the pivotal cells in the white matter. According to the literature, either oxidative stress or deposition of unfolded proteins cause OLs damage in dementia. On the other hand, dementia is ameliorated by proliferation and differentiation of the oligodendrocytes precursors (OLP) or preventing these cells from death. Therefore, showing the OLs' structure and function during various types of dementia can open a new window for researchers to conduct further investigations.
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Stroke is the second cause of death and disability in the world. Cell therapy can be considered as a suitable option due to its ability to restore and replace damaged neurons. Mouse embryonic stem cells (mESCs) were considered as potential candidates for the present research due to the release of growth and neurotrophic factors.

Rats were divided into three main groups: Intact, control, and mouse embryonic stem cell (mESCs) transplant recipients. In mESCs group, ischemia was induced by middle cerebral artery occlusion (MCAO) method four days after injection of half a million cells into striatum of rat brain by stereotaxic method. Rats were divided into subgroups to investigate neurological deficits, infarct volume, blood-brain barrier integrity, edema, superoxide dismutase (SOD) enzyme activity, and the expression of glutamate ionotropic receptor (GRIN1) and nitric oxide synthase (NOS1) genes.

A significant reduction in neurological deficits, infarct volume, blood-brain barrier damage and edema was observed in the mESCs group compared to the control group. Also, the expression of GRIN1 and NOS1 showed a significant decrease in the mESCs group compared to the control group. In addition, a significant increase in SOD enzyme expression was observed in the mESCs group compared to the control group.

The present results showed that transplantation of mESCs reduced ischemic damages. This effectiveness is probably due to reduction of inflammatory and excitotoxicity related-genes and increase of antioxidant enzyme.

Chronic low-grade inflammation is a common condition in obesity. The aim of the present study was to investigate the effects of aged garlic extract and aerobic training on TLR4/NFƙB inflammatory signaling pathway gene expression in obese male rats.

Forty male Sprague-Dawley rats were subjected to high-fat diet (n = 32) and standard diet group (n = 8) for 9 weeks. After inducing obesity in the rats fed high-fat diet, the rats of this group were divided into four subgroups (n = 8), including the obese control (OC), the supplemented with aged garlic extract (AGE), the aerobic training (AT), and the supplemented with aged garlic extract + aerobic training (AGE + AT). The rats in the standard diet group also continued their diet for 8 weeks and interventions continued for 8 weeks. AGE was fed to rats once daily at a dose of 600 mg/kg by gavage. AT also included running on a treadmill five days a week. The TLR4 and NFƙB gene expression was measured by Real-time PCR and lipid profile changes evaluated in plasma.

All interventions led to a significant decrease in TLR4 and NFƙB gene expression in visceral fat, as well as improving the lipid profile of obese rats (p = 0.001). TLR4 reduction was higher in AGE + AT group (p = 0.001). On the other hand, AGE and AGE + AT caused a greater decrease in NFƙB gene expression compared to AT (p = 0.001). AGE + AT also improved the lipid profile more compared to other interventions (p = 0.001).

The combining of interventions is more effective in reducing TLR4 and NFƙB gene expression in visceral fat as well as improving lipid profile.

Polycystic Ovary Syndrome is one of the common endocrine disorders in women caused by an increase in testosterone. Aromatase enzyme decreases testosterone. In the present study, the effect of drug Pramipexol as dopamine agonist in three doses and two different times on ovarian aromatase gene expression in Wistar PCOS rats was investigated.

Thirty mice were divided to two groups (n = 15) including three subgroups of solvent, PCOS (injection of 2 mg of Estradiol valerate), and PCOS + drug (1, 2, 4 mg/kg). Pramipexol was administered 15 or 30 days after induction of PCOS, as group 1 or 2, for 14 days. Aromatase gene expression was then measured, and analyzed by One-way ANOVA analysis of variance and Tukey's post hoc test.

The results showed an increase in aromatase gene expression in the subgroups receiving the drug (p < 0.05, p < 0.01, p < 0.001) in each of the two study groups. There was significant difference between 2 groups in gene expression after drug treatment by 2, and 4 mg/kg (p < 0.01, p < 0.05).

Pramipexol doses 1, 2, 4 mg/kg increased the expression of the ovarian aromatase gene in PCOS mice in a time and dose-dependent manner. Pramipexol 4 mg/kg, 15 days after induction of PCOS caused the greatest increase in aromatase gene expression and can be suggested to improve PCOS.
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Dopamine and noradrenaline  play an important role in food intake control. On the other hand, neuromedin S (NMS) decreases food intake. This study aimed to investigate the synergistic effects of dopamine and noradrenaline  with a sub-effective dose of NMS on food intake in neonatal chickens.

A total of 132 five-old-day chicks were randomly divided into three experimental groups. Each experiment had a control group and three treatment groups (n = 11 in each group). Three-hour food-deprived birds received intracerebroventricular ‎injections of either control diluent or drug solution. In the first experiment, control solution, NMS (0.25 nmol), L-DOPA (dopamine precursor; 125 nmol), and NMS + L-DOPA were injected.‎  In the second experiment, control solution, NMS (0.25 nmol), dopamine (10 nmol), and NMS + dopamine were injected. In the third experiment, control solution, NMS (0.25 nmol), noradrenaline (37.5 nmol), and , NMS + noradrenaline were injected.

Although the injection of NMS with a dose of 0.25 (sub-effective dose), L-dopa with a dose of 125 (sub-effective dose), dopamine with a dose of 10 (sub-effective dose), and noradrenaline with a dose of 37.5 (sub-effective dose) had no effect on food intake (p < 0.05), the co-injection of Neuromedin S with L-dopa or dopamine or noradrenaline decreased food intake (p < 0.05).

According to the results of the present study, there is probably a synergistic effect between NMS with dopamine and noradrenaline on food intake control of neonatal chicks.

Noradrenergic system is involved in stress and anxiety related behaviors. The neural pathways of stress and the noradrenergic system in the hippocampus have a reciprocal effect on each other. Therefore, in this study, the effect of noradrenergic activity on anxiety and learning under stress conditions is investigated.

Adult male Wistar rats weighing 180-230 were given acute (3 days) or chronic (21 days) restrained stress. Yohimbine was injected with a dose of 2 mg/kg (intraperitoneally) to activate the noradrenergic system. After 24 hours from the last stress session, social learning and then anxiety and exploratory behavior and new object recognition were investigated in animals.

The amount of association with a familiar rat (stranger 1) decreased due to acute (p < 0.01) and chronic
(p < 0.001) stress and increased with a stranger rat (stranger 2). The time in the open arm of the elevated plus maze decreased (p < 0.001) due to acute and chronic stress, and animals receiving yohimbine, while the time increased
(p < 0.001) in the closed arm. The duration of immobility in the open field test increased due to acute (p < 0.01) and chronic (p < 0.001) stresses, while it decreased after yohimbine administration in the chronic (p < 0.001) stress group. The time spent with the familiar object was increased (p < 0.001) by chronic stress and decreased (p < 0.001) by acute stress and yohimbine administration.

This study showed that increasing the activity of the noradrenergic system moderates the effects of chronic stress, which indicates the possible cooperation of the glucocorticoid and adrenergic systems.

The endothelium layer plays an important role in maintaining vascular homeostasis. The activation and dysfunction of endothelial cells is one of  the first detectable changes in atherosclerosis as one of the macro-vascular complications of diabetes. In this study, according to the physiological function of G-protein coupled receptors in the vascular system, the changes in gene expression of two receptors, ADGRF5 and ADGRL4 were investigated in hyperglycemic conditions and the use of atorvastatin.

Endothelial cells were transferred from normal conditions to hyperglycemic environment and kept in these conditions for 48, 24 and 72 hours. In hyperglycemic conditions, the cells were treated with atorvastatin (5 and 10 µM) for 24 hours. The expression of target genes was measured in hyperglycemic conditions and under atorvastatin treatment, scratch test cell culture was performed in the presence of atorvastatin drug.

ADGRF5 and ADGRL4 gene expression decreased significantly p ≤ 0.01 in hyperglycemic environment at 24, 48 and 72 hours, the level decreased by about 7 to 9.5 times and about 7 to 28 times respectively for genes. Treatment with atorvastatin in hyperglycemic conditions resulted in a significant increase in the expression of receptors p ≤ 0.01. VEGFA and DLL4 showed a significant decrease in expression compared to hyperglycemic conditions. An increase in the power of cell movement and changes in the morphology of cells were observed when using atorvastatin.

Changes in the expression of ADGRF5 and ADGRL4 receptors in hyperglycemic conditions can focus on the role of these receptors in the process of angiogenesis in vascular disorders, which is useful for future studies related to vascular disorders related to diabetes complications.
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5-Hydroxytryptamine or serotonin is a biogenic amine that is best known for its function as a neurotransmitter. One of the most important effects of serotonin is its role in regulating food intake. Further understanding of the serotonergic mechanisms affecting food consumption, in addition to improving animal production, can lead to effective serotonin-based drug treatments to help modulate appetite in humans. The purpose of this review is to examine the research conducted on the role of the serotonergic system (except for the interference of its effect with other systems) in the process of obtaining food. In the present study, according to PRISMA guidelines, articles related to the topic were identified using a systematic search of standard keywords in reliable databases such as Web of Science, Scopus, Science Direct, PubMed, Springer, Google Scholar, and Elsevier in the period of 1990-2022. In order to obtain more studies, the list of sources of these articles was examined. Finally, 40 articles that met all the conditions for entering the analytical stage were examined. Based on the findings of these studies, serotonin in birds and mammals reduces food intake. Serotonin reuptake inhibitor compounds also cause hypophagia and serotonin receptor agonists and antagonists have different effects on the appetite process. It also seems that 5HT1A, 5HT1B and 5HT2C receptors have the most interaction in the process of appetite modulation. Considering the diversity of serotonin receptors and the distribution of this system in different central and peripheral areas in order to know its role in regulating food intake, it is necessary to carry out more research in this field.
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Melilotus officinalis (Papilionaceae family) possess potent antioxidant, anxiolytic, anti-inflammatory, and anticonvulsant activities. According to the mentioned cases, the aim of the current study was to investigate the antidepressant effect of the M. officinalis ethanolic extract (MOEE) in the murine models.

In this study, the acute toxicity of the MOEE was evaluated by Lorek's method. Adult male NMRI mice were treated with normal saline, fluoxetine (20 mg/kg, i.p.), or MOEE (50, 100, and 200 mg/kg, i.p.), and then it was performed to forced swimming test(FST) and tail suspension test (TST).  The locomotion of the mice was also evaluated in the open-field test (OFT).

The results showed that the LD50 of the extract was found to be greater than 5000 mg/kg. Intraperitoneal administration of MOEE (except the dose of 25 mg/kg in FST)  reduces immobility time in all groups of the FST and TST. Also, this extract increased the duration of swimming time without significant change in the climbing time in the FST. The locomotion of mice was not affected by the MOEE in OFT.

The results of this study show that Melilotus officinalis is a non-toxic compound and has antidepresant activity similar to fluoxetine. Therefore, this plant has therapeutic potential for depression. However, more studies are necessary to determine the exact mechanism of the anti-depressant effect and the absence of adverse effects in chronic administration.
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