Protective Effects of Long-Term Escitalopram Administration on Memory and Hippocampal BDNF and BCL-2 Gene Expressions in Rats Exposed to Predictable and Unpredictable Chronic Mild Stress.

Stress and escitalopram (an anti-stress medication) can affect brain functions and related gene expression. This study investigated the protective effects of long-term escitalopram administration on memory, as well as on hippocampal BDNF and BCL-2 gene expressions in rats exposed to predictable and unpredictable chronic mild stress (PCMS and UCMS, respectively). Male rats were randomly assigned to different groups: control (Co), sham (Sh), predictable and unpredictable stress (PSt and USt, respectively; 2 h/day for 21 consecutive days), escitalopram (Esc; 10 mg/kg for 21 days), and predictable and unpredictable stress with escitalopram (PSt-Esc and USt-Esc, respectively). The passive avoidance test was used to assess behavioral variables. The expressions of the BDNF and BCL-2 genes were assessed using real-time quantitative PCR. Latency significantly decreased in the PSt and USt groups. Additionally, latency showed significant improvement in the PSt-Esc group compared to the PSt group. The expression of the BDNF gene significantly decreased only in the USt group. BDNF gene expression significantly increased in the PSt-Esc and USt-Esc groups compared to their respective stress-related groups, whereas the expression of the BCL-2 gene did not change significantly in both PSt-Esc and USt-Esc groups. PCMS and UCMS had devastating effects on memory. Escitalopram improved memory only under PCMS conditions. PCMS and UCMS exhibited fundamental differences in hippocampal BDNF and BCL-2 gene expressions. Furthermore, escitalopram increased hippocampal BDNF gene expression in the PCMS and UCMS subjects. Hence, neurogenesis occurred more significantly than anti-apoptosis under both PCMS and UCMS conditions with escitalopram.

Effects of chronic social equality and inequality conditions on passive avoidance memory and PTSD-like behaviors in rats under chronic empathic stress.

INTRODUCTION: Social inequality conditions induce aversion and affect brain functions and mood. This study investigated the effects of chronic social equality and inequality (CSE and CSI, respectively) conditions on passive avoidance memory and post-traumatic stress disorder (PTSD)-like behaviors in rats under chronic empathic stress. METHODS: Rats were divided into different groups, including control, sham-observer, sham-demonstrator, observer, demonstrator, and co-demonstrator groups. Chronic stress (2 h/day) was administered to all stressed groups for 21 days. Fear learning, fear memory, memory consolidation, locomotor activity, and PTSD-like behaviors were evaluated using the passive avoidance test. Apart from the hippocampal weight, the correlations of memory and right hippocampal weight with serum corticosterone (CORT) levels were separately assessed for all experimental groups. RESULTS: Latency was significantly higher in the demonstrator and sham-demonstrator groups compared to the control group. It was decreased significantly in other groups compared to the control group. Latency was also decreased in the observer and co-demonstrator groups compared to the demonstrator group. Moreover, the right hippocampal weight was significantly decreased in the demonstrator and sham-demonstrator groups compared to the control group. Pearson's correlation of memory and hippocampal weight with serum CORT levels supported the present findings. CONCLUSION: Maladaptive fear responses occurred in demonstrators and sham-demonstrators. Also, extremely high levels of psychological stress, especially under CSI conditions (causing abnormal fear learning) led to heightened fear memory and PTSD-like behaviors. Right hippocampal atrophy confirmed the potential role of CSI conditions in promoting PTSD-like behaviors. Compared to inequality conditions, the abnormal fear memory was reduced under equality conditions.

Effects of sub-chronic CRH administration into the hypothalamic paraventricular and central amygdala nuclei in male rats with a focus on food intake biomarkers.

CRH neurons are found in the paraventricular nucleus(PVN) and central amygdala(CeA) nuclei. This study investigated the effects of sub-chronic CRH administration into the PVN and CeA nuclei on food intake biomarkers in rats divided into five groups: control, two shams, and two CRH-PVN and CRH-CeA groups(receiving CRH in nuclei for seven days). The CRH-PVN group had significantly higher cumulative food intake and food intake trends than the CRH-CeA group. The CRH-CeA and CRH-PVN groups exhibited significant increases in food intake during hours 1 and 2, respectively. Moreover, to be time-dependent, food intake is modulated by different brain nuclei. The CRH signaling pathway appeared to be activated later in the PVN than CeA. Both groups exhibited significantly higher leptin levels, the CRH-PVN group exhibited higher ghrelin levels and lower glucose levels. Repetitive administration of CRH into the PVN and CeA significantly reduced body weight differences. CRH administration into the PVN affected both leptin and ghrelin levels, but ghrelin had a greater impact on glucose variations and cumulative food intake than leptin. Finally, CRH administration into the PVN and CeA likely activated the HPA axis, and the CeA had a greater impact on the stress circuit than on food intake behavior.

Effects of Aqueous Saffron Extract on Glucoregulation as Well as Hepatic Agt and TNF-α Gene Expression in Rats Subjected to Sub-Chronic Stress.

Background: Stress and saffron seem to affect glucoregulation mechanisms and insulin resistance in different ways. Impacts of the aqueous saffron extract were investigated on serum glucose levels, serum insulin levels, the homeostatic model assessment of ß-cell function (HOMA-B), the homeostatic model assessment of insulin resistance (HOMA-IR), adrenal weight, and hepatic gene expression of angiotensinogen (Agt) and tumor necrosis factor-α (TNF-α) in rats under sub-chronic stress. Materials and Methods: Forty-two male rats were divided into six groups: control, restraint stress (6h/day for seven days), saffron (30 and 60 mg/kg) treatments for seven days, and post-stress saffron (30 and 60 mg/kg) treatments for seven days. The serum glucose and insulin levels, hepatic gene expressions of Agt and TNF-α, HOMA-IR, HOMA-B, and adrenal gland weight were measured. Results: One-week recovery following sub-chronic stress led to non-significant hyperglycemia, hyperinsulinemia, and insulin resistance. The hepatic Agt and TNF-α mRNA levels increased significantly in this group. Saffron administration led to enhanced hepatic Agt mRNA in the non-stressed subjects. In addition, serum glucose levels, insulin resistance, and hepatic Agt gene expression significantly increased in stress-saffron groups. The hepatic TNF-α gene expression was reduced only in the stress-saffron 60 group. Conclusion: Saffron treatment after sub-chronic stress not only did not improve glucose tolerance but also enhanced insulin resistance. It indicated the interaction of saffron and sub-chronic stress to promote renin-angiotensin system activity. In addition, the saffron treatment decreased TNF-α gene expression after sub-chronic stress. The synergistic stimulating effect of saffron and sub-chronic stress on gene expression of hepatic Agt led to insulin resistance and hyperglycemia.

In vivo synaptic potency, short-term and long-term plasticity at the hippocampal Schaffer collateral-CA1 synapses: Role of different light-dark cycles in male rats.

The changes in the light-dark(L/D) cycle could modify cellular mechanisms in some brain regions. The present study compared the effects of various L/D cycles on invivo synaptic potency, short-term and long-term plasticity in the hippocampal CA1 area, adrenal glands weight(AGWs), corticosterone (CORT) levels, and body weight differences(BWD) in male rats. Male rats were assigned into different L/D cycle groups: L4/D20, L8/D16, L12/D12(control), L16/D8, and L20/D4. The slope, amplitude, and the area under curve(AUC) related to the field excitatory postsynaptic potentials(fEPSPs) were assessed, using the input-output(I/O) functions, paired-pulse(PP) responses at different interpulse intervals, and after the induction of long-term potentiation(LTP) in the hippocampal CA1 area. Also, the CORT levels, AGWs, and BWDs were measured in all groups. The slope, amplitude, and AUC of fEPSP in the I/O functions, all three phases of PP, before and after the LTP induction, were significantly decreased in all experimental groups, especially in the L20/D4 and L4/D20 groups. As such, the CORT levels and AGWs were significantly increased in all experimental groups, especially in the L20/D4 group. Overall, the uncommon L/D cycles (minimum and particularly maximum durations of light) significantly reduced the cellular mechanism of learning and memory. Also, downtrends were observed in synaptic potency, as well as short-term and long-term plasticity. The changes in PP with high interpulse intervals, or activity of GABAB receptors, were more significant than the changes in other PP phases with different L/D durations. Additionally, the CORT levels, adrenal glands, and body weight gain occurred time-independently concerning different L/D lengths.

The impact of different dark chocolate dietary patterns on synaptic potency and plasticity in the hippocampal CA1 area of the rats under chronic isolation stress.

INTRODUCTION: Although, stress causes brain dysfunction, consumption of dark chocolate (DC) has positive effects on brain functions. The current study investigated the impact of different DC dietary patterns on synaptic potency and plasticity in the hippocampal CA1 area, as well as food intake and body weight in rats under chronic isolation stress. METHODS: Thirty-five rats were allocated into five groups of control, stress, and stress accompanied by three DC dietary patterns (stress-compulsory, -optional, and -restricted DC). The stressed rats on a compulsory diet only received DC and the ones on an optional diet received unlimited chow and/or DC. Also, the stressed rats on a restricted diet each received chow freely and only 4 g DC daily. Subsequently, the slope and amplitude of field excitatory postsynaptic potentials (fEPSPs) were assessed based on the Input-Output (I/O) curves and after the longterm potentiation (LTP). Moreover, food intake and body weight were measured for all groups. RESULTS: The fEPSP slope and amplitude in the I/O curves and after LTP decreased significantly in the stress group compared to the control group. Although the slope and amplitude both enhanced non-significantly in the optional DC diet, these parameters changed significantly in both compulsory and restricted DC dietary patterns compared to the stress group. Also, food intake and body weight decreased significantly in all DC groups. CONCLUSION: The compulsory and restricted DC dietary patterns reversed the harmful effects of chronic isolation stress on the hippocampal synaptic potency, plasticity, learning, and memory. All DC diets, especially compulsory and restricted ones, reduced food intake and body weight.

Therapeutic effects of exercise-accompanied escitalopram on synaptic potency and long-term plasticity in the hippocampal CA1 area in rats under chronic restraint stress.

Objectives: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.

The Protective Effects of Crocin on Input-Output Functions and Long-term Potentiation of Hippocampal CA1 Area in Rats Exposed to Chronic Social Isolated Stress.

Introduction: The lack of social communication is associated with the primary risk of proper brain functions. It is reported that crocin helps relieve this problem. The present study examined the protective effect of two doses of crocin on Long-term potentiation (LTP) of hippocampal cornu ammonis 1 (CA1) area as a cellular mechanism in rats exposed to chronic social isolated stress. Methods: Rats were assigned to the control, sham, isolation stress, and two stress groups (receiving 30 and 60 mg/kg crocin). Chronic isolation stress (CIS) was induced 6 h/d, and crocin was administrated for 21 days. The field excitatory postsynaptic potential (fEPSP) slope and amplitude were measured by input/output functions and LTP induction in the CA1 area of the hippocampus. Also, the corticosterone and glucose levels were assayed in the hippocampus and frontal cortex. Results: The slope and amplitude of fEPSP severity were impaired in both input/output and LTP responses in the CIS group. Crocin at a dose of 30 and particularly 60 mg/kg improved input/output and LTP responses in the CIS group. Also, the corticosterone levels significantly increased in the frontal cortex and especially the hippocampus. In contrast, only a high dose of crocin decreased hippocampal corticosterone levels in the CIS condition. Finally, the glucose levels did not change in the hippocampus and frontal cortex in all experimental groups. Conclusion: The chronic isolation stress impaired neural excitability and Long-term plasticity in the CA1 area due to elevated corticosterone in the hippocampus and probably the frontal cortex. The low and high doses of crocin improved excitability and Long-term plasticity in the chronic isolation stress group by only decreasing corticosterone levels in the hippocampus, but not the frontal cortex. Highlights: Neuronal excitability and long-term plasticity of CA1 were impaired by chronic isolation stress.The memory was protected by low and particularly high doses of crocin in the chronic isolation stress condition.Crocin decreased the corticosterone levels in hippocampus, but not frontal cortex. Plain Language Summary: The lack of social communication (isolation stress) is associated with the primary risk of brain functions. On the other hand, crocin as one of effective components of saffron is helpful for improvement of memory. Therefore, the protective effect of two doses of crocin on cellular mechanism of memory in rats exposed to chronic social isolated stress was investigated in present study. Chronic isolation stress (CIS) was induced 6h/day, and crocin was administrated for a period of 21 days at two doses of 30 and 60 mg/kg. The electrophysiological and cellular mechanism of memory in the CA1 area of the hippocampus were investigated. Also, the corticosterone and glucose levels were assayed in the hippocampus and frontal cortex. It was concluded that the chronic isolation stress impaired neural excitability and long-term plasticity in the CA1 area due to elevated corticosterone in the hippocampus and probably the frontal cortex. The low and high doses of crocin improved excitability and long-term plasticity in the chronic isolation stress group by only decreasing corticosterone levels in the hippocampus, but not the frontal cortex. Also, the corticosterone levels significantly increased in the frontal cortex and especially the hippocampus. Also, the glucose levels did not change in the hippocampus and frontal cortex in all experimental groups.

The protective effects of escitalopram on synaptic plasticity in the CA1 region of chronically stressed and non-stressed male rats.

INTRODUCTION: Stress impairs cognitive processes and escitalopram affects them in various ways. The present study has compared the protective effects of two escitalopram doses on neural excitability and synaptic plasticity in the CA1 region of chronically stressed and non-stressed male rats. METHODS: Forty-nine rats were randomly allocated into seven groups: Control (Co), stress (St), sham (Sh), escitalopram 10 and 20 mg/kg (Esc10 and Esc20), and stress-escitalopram 10 and 20 mg/kg (St-Esc10 and St-Esc20). Induction of restraint stress (6 h/day) and escitalopram injections were performed for 14 days. The fEPSP slope and amplitude were measured according to input-output functions and after the LTP induction in the hippocampal CA1 region. Also, serum corticosterone levels were evaluated in all experimental groups. RESULTS: The fEPSP slope and amplitude decreased significantly in the St group and increased significantly in the Esc10 group compared with the Co group. In non-stressed states, significant increases in slope and amplitude occurred in the Esc10 group compared with the Esc20 group. Notably, these values were also significantly enhanced by both escitalopram doses under stressed conditions. Moreover, serum corticosterone levels significantly elevated in the St group although its levels decreased in both St-Esc groups compared with the St. CONCLUSION: Stress significantly attenuated neural excitability and long-term plasticity in the CA1 area. Only escitalopram 10 mg/kg improved synaptic excitability, as well as LTP induction and maintenance in non-stressed subjects even more than normal levels. However, under stress conditions, both escitalopram doses enhanced neural excitability and memory probably due to reduced serum corticosterone levels.

Preventive effects of fixed and progressive forced exercises on memory and brain electrical activity in morphine-addicted rats.

Exercise and addiction influence brain functions. The preventive effects of fixed and progressive forced exercises on both brain functions and body weight were investigated in morphine-addicted rats. Thirty-five rats were allocated to control, morphine, fixed exercise-morphine, and progressive exercise-morphine groups. Forced exercise was applied 1h/day for 21 days with morphine sulfate administered at doses of 10, 20, 30, 40, and 50 mg/kg for 5 consecutive days. The 50 mg/kg dose was repeated over the five subsequent days. Brain performance was evaluated using the passive avoidance test and EEG recordings. The passive avoidance test revealed no significant changes in brain functions (namely, latency, total dark stay time, and number of times entering the dark compartment). Compared to the control, the morphine group exhibited significantly lower alpha and beta waves but significantly higher delta and theta ones. Compared to the morphine group, the progressive and fixed exercise-morphine groups exhibited significant changes in their passive avoidance performance and only in the alpha wave of their EEG recordings. Progressive exercise improved learning, memory, and memory consolidation but reduced locomotor activity whereas fixed exercise affected EEG recordings in the addicted subjects. Clearly, different (fixed or progressive) exercise models produced different changes in brain functions.

Overview of the central amygdala role in feeding behaviour.

The neural regulation of feeding behaviour, as an essential factor for survival, is an important research area today. Feeding behaviour and other lifestyle habits play a major role in optimising health and obesity control. Feeding behaviour is physiologically controlled through processes associated with energy and nutrient needs. Different brain nuclei are involved in the neural regulation of feeding behaviours. Therefore, understanding the function of these brain nuclei helps develop feeding control methods. Among important brain nuclei, there is scant literature on the central amygdala (CeA) nucleus and feeding behaviour. The CeA is one of the critical brain regions that play a significant role in various physiological and behavioural responses, such as emotional states, reward processing, energy balance and feeding behaviour. It contains γ-aminobutyric acid neurons. Also, it is the major output region of the amygdaloidal complex. Moreover, the CeA is also involved in multiple molecular and biochemical factors and has extensive connections with other brain nuclei and their neurotransmitters, highlighting its role in feeding behaviour. This review aims to highlight the significance of the CeA nucleus on food consumption by its interaction with the performance of reward, digestive and emotional systems.

Therapeutic effects of saffron extract on different memory types, anxiety, and hippocampal BDNF and TNF-α gene expressions in sub-chronically stressed rats.

Objective: While stress reportedly impairs memory, saffron enhances it. This study investigated the therapeutic effects of saffron extract on different memory types, anxiety-like behavior, and expressions of BDNF and TNF-α genes in sub-chronically stressed rats.Methods: Rats were randomly assigned to control, restraint stress (6 h/day/7 days), two 7-days saffron treatments with 30 and 60 mg/kg, and two stress-saffron groups (30 and 60 mg/kg/7 post-stress days). Serum cortisol level and hippocampal BDNF and TNF-α gene expressions were measured. Open field, passive avoidance, novel object recognition, and object location tests were performed to assess anxiety-like behavior and avoidance as well as cognitive and spatial memories, respectively.Results: The low saffron dose in the sub-chronic stressed group led to a significant increase in passive avoidance latency from day 3 onward whereas this effect was observed after 7 days under the high-dose treatment that simultaneously led to a significant decline in serum cortisol level. While the low saffron dose led to a sharp drop in hippocampal TNF-α gene expression, the high dose significantly increased the hippocampal BDNF gene expression in the sub-chronic stress group. Finally, both saffron doses reduced anxiety in the stressed groups.Conclusion: Compared to the low saffron dose, the high dose had a latent but long-lasting impact. Cognitive and spatial memories remained unaffected by either stress or saffron treatment. In addition, only the high saffron dose reversed anxiety in the sub-chronically stressed group. These findings suggest that various doses of saffron act differently on different brain functions under sub-chronic stress conditions.Abbreviations: Brain derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), hypothalamic-pituitary-adrenal axis (HPA), novel object recognition task (NORT), novel object location task (NOLT), open field test (OFT), passive avoidance (PA).

Comparing the Therapeutic Effects of Crocin, Escitalopram and Co-Administration of Escitalopram and Crocin on Learning and Memory in Rats with Stress-Induced Depression.

BACKGROUND: Depression affects various brain functions. According to previous studies, escitalopram influences brain functions in depression and crocin reduces memory impairments. Therefore, this study aimed to compare the therapeutic effects of using crocin and escitalopram (separately and in combination) on learning and memory in rats with stress-induced depression. METHODS: Fifty-six rats were allocated into seven groups of control, sham, continuous depression, recovery period, daily injections of escitalopram, crocin and escitalopram-crocin during 14 days after inducing depression by stress. Passive avoidance (PA) test was used to assess brain functions. RESULTS: Latency has significant differences in depression group. Also, it significantly increased in depression-crocin, depression-escitalopram and depression-escitalopram-crocin groups compared to the depression group. The dark stay (DS) time was significantly higher in the depression and depression-recovery groups. However, the DS time significantly decreased in the depression-crocin, depression-escitalopram and depression-escitalopram-crocin groups. Furthermore, the number of entrances to the dark room was significantly lower in depression-crocin and depression-escitalopram-crocin groups compared to the depression one. CONCLUSION: Different depression treatments (i.e. crocin, escitalopram and crocin-escitalopram) reduced depression-induced memory deficits. Crocin and escitalopram-crocin, respectively, improved brain functions and locomotor activity more than escitalopram. Comparatively, in subjects with depression, crocin, which is an effective saffron constituent, partially affected the memory deficits better than escitalopram (as a chemical component).

Comparing the effects of crocin at different doses on excitability and long-term potentiation in the CA1 area, as well as the electroencephalogram responses of rats under chronic stress.

Stress adversely affects the cellular and electrophysiological mechanisms of memory; however, crocin has beneficial effects on brain functions. Nonetheless, the electrophysiological effects of using this active saffron component at different doses are not yet studied in rats under chronic restraint stress. Therefore, this study compared the impact of crocin at different doses on the excitability and long-term potentiation (LTP) in the CA1 area of rats, as well as their electroencephalogram (EEG) responses, hippocampal and frontal cortical glucose levels under chronic restraint stress (an emotional stress model). Forty rats were allocated into five groups of control, sham, restraint stress (6 h/day/21 days), and two stress groups receiving intraperitoneal injections of crocin (30, 60 mg/kg/day). Besides measuring the slope and amplitude of field excitatory postsynaptic potentials (fEPSPs) in the input-output and LTP curves, the EEG waves and hippocampal and frontal cortical glucose levels were assessed in all groups. Chronic restraint stress significantly decreased the fEPSP slope and amplitude in the input-output curves and after LTP induction. Both doses of crocin (60 and particularly 30 mg/kg) significantly improved fEPSP slope and amplitude in the stressed groups. Also, stress and crocin only at a dose of 30 mg/kg altered the EEG waves. Hippocampal and frontal cortical glucose levels displayed no significant differences in the experimental groups. Crocin at doses of 60 mg/kg/day and particularly 30 mg/kg/day reversed the harmful effects of chronic restraint stress on LTP as a cellular memory-related mechanism. However, only the lower dose of crocin affected the electrical brain activity in EEG.

Possible involvement of the dopamine D2 receptors of ventromedial hypothalamus in the control of free- and scheduled-feeding and plasma ghrelin level in rat.

OBJECTIVES: We investigated effect of the ventromedial hypothalamus (VMH) dopamine D2 receptor inhibition on food intake and plasma ghrelin following chronic free or scheduled meal with different caloric intakes. METHODS: Male Wistar rats (220-250 g) were fed diets containing free (control) or three scheduled diets of standard, restricted and high-fat for 1 month. The animals stereotaxically received an intra VMH single dose of sulpiride (0.005 µg)/or saline (0.5 µL) before meal time. Thirty minutes later, food intake and circulating ghrelin were measured. RESULTS: Sulpiride significantly reduced food intake and ghrelin concentration in freely fed and scheduled-standard diet (p<0.05), while increased food intake, with ghrelin level on fasted level in scheduled-restricted group (p<0.01) compared to control. Food intake and ghrelin concentration between scheduled-high fat and freely fed or scheduled-standard diets did not show significant changes. CONCLUSIONS: The VMH D2 receptors are possibly involved in controlling scheduled eating behavior, depending on energy balance context.

ComparativeStudyofCRHMicroinjections Into PVN and CeA Nuclei on Food Intake, Ghrelin, Leptin, and Glucose Levels in Acute Stressed Rats.

INTRODUCTION: Corticotropin-Releasing Hormone (CRH) is involved in stress and energy homeostasis. On the other hand, CRH receptors also exist within the paraventricular nucleus (PVN) and Central Amygdala (CeA) nuclei. The present study compared the effect of CRH microinjections into PVN and CeA on three consecutive hours and cumulative food intake, internal regulatory factors of food intake, such as serum leptin and ghrelin, as well as blood glucose levels in rats under different acute psychological (Social Stress [SS] and Isolation Stress [IS] group) stresses. METHODS: Sixty-six male Wistar rats were randomly allocated to 11 groups: Control, Sham, CRH-PVN, CRH-CeA, SS, IS, SS-CRH-PVN, SS-CRH-CeA, IS-CRH-PVN, and IS-CRH-CeA groups. The CRH (2 µg/kg in 0.5 µL saline) was injected into PVN and CeA nuclei in rats under everyday, acute social stress and isolation stress conditions. RESULTS: Acute isolation and social stresses did not affect cumulative food intake. Whereas isolation stress led to changes in both leptin and glucose levels, social stress reduced only glucose levels. Cumulative food intake significantly decreased under acute CRH injection into the CeA and particularly into the PVN. Blood glucose significantly reduced in all the groups receiving CRH into their CeA. CONCLUSION: The PVN played a more important role compared to CeA on food intake. These nuclei probably employ different mechanisms for their effects on food intake. Besides, it seems that exogenously CRH injection into the PVN probably had a more anorectic effect than naturally activated CRH by stresses. Acute isolation stress had a greater impact than social stress on leptin level and cumulative food intake. Thus, elevated food intake related to leptin compared to ghrelin and glucose levels in the CRH-PVN group under acute social stress.

The effects of concurrent treatment of silymarin and lactulose on memory changes in cirrhotic male rats.

Introduction: Chronic liver disease frequently accompanied by hepatic encephalopathy (HE). Changes in the permeability of the blood-brain barrier in HE, make an easier entrance of ammonia among other substances to the brain, which leads to neurotransmitter disturbances. Lactulose (LAC), causes better defecation and makes ammonia outreach of blood. Silymarin (SM) is a known standard drug for liver illnesses. The purpose of this research was to determine the results of LAC and SM combined treatment, on the changes in memory of cirrhotic male rats. Methods: The cirrhotic model established by treatment with thioacetamide (TAA) for 18 weeks. Cirrhotic rats randomized to four groups (n = 7): TAA group (received drinking water), LAC group (2 g/kg/d LAC in drinking water), SM group (50 mg/kg/d SM by food), SM+ LAC group (similar combined doses of both compounds) for 8 weeks. The control group received drinking water. The behavior examined by wire hanging (WH), passive avoidance (PA), and open field (OF) tests. Results: Our findings showed that treatment with SM+LAC effectively increased PA latency, compared with the control group. The results showed that the administration of LAC and SM+LAC affected the number of lines crossed, the total distance moved and velocity in the OF tests. Conclusion: SM and LAC have anti-inflammatory effects that are memory changing. It may be due to their useful effects. These results indicated that SM+LAC restored memory disturbance and irritated mood in the cirrhotic rats. Comparable neuroprotection was never previously informed. Such outcomes are extremely promising and indicate the further study of SM+LAC.

Comparative study of the protective effects of crocin and exercise on long-term potentiation of CA1 in rats under chronic unpredictable stress.

Aim While stress causes brain dysfunction, crocin (as an active component of saffron) and exercise (as part of a healthy lifestyle) improve stress-induced memory impairment. The present study investigated the protective effects of crocin administration, exercise, and crocin-accompanied exercise on neuronal excitability and long-term potentiation (LTP) at the CA1 of hippocampus as well as serum corticosterone and glucose levels in rats subjected to chronic unpredictable stress (CUS). MAIN METHODS: Forty-eight male Wistar rats were randomly allocated to six groups: Control, Sham, CUS, CUS-Crocin30, CUS-Exercise, and CUS-Crocin30-Exercise. The chronic unpredictable stress and treadmill running at 20-21 m/min were applied 2 h/day and 1 h/day, respectively, for 21 days. Crocin (30 mg/kg) was daily intraperitoneally injected to the rats. Electrophysiological variables were recorded from the CA1 of hippocampus. While corticosterone and glucose levels were also measured. KEY FINDINGS: CUS and CUS-Exercise significantly attenuated excitability and LTP. Compared to the CUS and CUS-Exercise treatments, CUS-Crocin30 and CUS-Crocin30-Exercise led to significant increases in slope and amplitude of field excitatory postsynaptic potential. The changes in serum corticosterone and glucose levels nearly matched the electrophysiological data. SIGNIFICANCE: CUS was found to be a highly destructive stress as it failed to allow exercises to edify the CUS-induced memory deficit. This is while crocin (as a herbal drug) was found more effective than exercise (as a daily routine) in remedying the CUS-induced memory deficit. Also, although the treatment with crocin-accompanied exercise did help recovery from the CUS-induced memory deficit, the interaction of crocin administration and exercise had no synergic effects; the protective effect observed was due to crocin administration rather than the exercise.

Electrical stimulation mPFC affects morphine addiction by changing glutamate concentration in the ventral tegmental area.

Morphine addiction is known as a serious social problem. Medial prefrontal cortex (mPFC) and ventral tegmental area (VTA) are two important sites of the brain that contribute to this type of addiction, and a complicated relation exists in between. In addition, neurotransmitters like glutamate and γ--Amino Butyric Acid (GABA) play an important role in the formation of these relations. Thus, the present study was undertaken to investigate these relations by evaluating the level of associated changes in the indicated neurotransmitters in the VTA, using HPLC method. This was performed after electrical stimulation and inducing lesion of mPFC and through microinjections of N-Methyl-D-Aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, respectively AP5 and CNQX, into the VTA of addicted rats. Our results showed that intra-peritoneal (i.p.) administration of morphine in 9 days in the morphine group, and also electrical stimulation (100 µA) of mPFC, receiving (i.p.) morphine, caused an increase in the glutamate release in the VTA, compared to the control group, but the increase of glutamate levels in the VTA in the morphine-stimulation group was not significant, compared to the morphine group. Moreover, GABA release into this area was decreasing in morphine and morphine- stimulation groups, compared to the control group. Our findings also showed that electrical lesion (0.4 mA) of mPFC, and also microinjection of glutamate antagonists into the VTA, receiving (i.p.) morphine in rats, caused a decrease of glutamate in the VTA. Therefore, it could be concluded that the relation between mPFC and VTA is highly effective in the formation of reward system.

Effect of Crocin, Exercise, and Crocin-accompanied Exercise on Learning and Memory in Rats under Chronic Unpredictable Stress.

BACKGROUND: 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). MATERIALS AND METHODS: 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: 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. CONCLUSION: 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.