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The main purpose of this systematic review was to evaluate the association between the stroke (risk of stroke and the mortality due to stroke) and vitamin A, its organic compounds and its provitamins.Major databases including PubMed, Scopus, and Web of Science were searched. Studies with human samples were included for risk assessment. The association was assessed using odds ratio (Twenty-one studies including 5789 stroke patients were retrieved. Twenty studies had sufficient information for quantitative analyses. The pooled effect showed an inverse association between vitamin A and its organic compound with the risk of stroke (Insufficiency of retinol and beta-carotene significantly increased the risk of stroke; however, due to heterogeneity between studies more studies are needed for evaluating clinical significance of this outcome.

Nowadays, high-fat foods are eaten in most societies, which causes memory impairment and anxiety through the oxidative stress pathway. Sesame oil (SO) has potential antioxidant properties. The hypothesis of this study was that sesame oil affect memory impairment and anxiety caused by a high-fat diet (HFD) in male rats. Eighty male Wistar rats were divided into eight groups (n = 10): control (standard diet; SD), the HFD, SD + SO (0.5, 1, or 2 ml/kg; once/day, gavage), and HFD + SO (0.5, 1, or 2 ml/kg; once/day, gavage) groups. All diets were given to the animals for three months. Finally, behavioral and oxidative stress parameters were measured. The step-through latency of retention test in SD + SO (0.5 or 1 ml/kg) groups increased more than the control group. Also, the Barnes test on training days revealed that the latency time to find the target hole increased in the HFD group compared with the control group. Moreover, the time spent on the open arms in the SD + SO (0.5 ml/kg) group improved remarkably than the control group. Total oxidant (TOS) level in the HFD + SO (0.5, 1, and 2 ml/kg) groups was lower than the HFD group. The level of total antioxidant capacity (TAC) in the SD + SO (2 ml/kg) group was higher than the SD + SO (0.5 ml/kg) group and the amount of thiol in the HFD group decreased compared with the control group. These findings suggest that the positive effects of SO on memory and anxiety are probably due to its antioxidant properties and the elimination of free radicals.

Aged heart is defined via structural and mitochondrial dysfunction of the heart. However, there is still no impressive compound to suppress and improve the abnormal alterations in cardiac function result from aging. Gallic acid (GA) is known to be an effective agent in improving cardiovascular disorders. In the present study, we exhibit the protective effects of GA against cardiac aging. Male Wistar rats were randomly divvied into four groups: Control, Control treated with GA at 25 mg/kg (GA25), aged rats induced by D-galactose (D-GAL), aged rats treated with GA at 25 mg/kg (D-GAL + GA25).Aging induced by D-GAL at 150 mL/kg via intraperitoneal injection for eight weeks. Aged rats treated with GA at 25 mg/kg (D-GAL GA25) by gavage for eight weeks. The blood samples were used to assessment biochemical factors and heart tissue was assessed for evaluating oxidative stress and the gene expression of molecular parameters. Histological examination of the heart was occurred. The D-GAL rats indicated cardiac hypertrophy, which was associated with reduced antioxidant activity of enzyme, increased oxidative marker and alterations in Sirtuin 1 (SIRT1), Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha and Transcription Factor A, Mitochondrial (TFAM) genes expression in comparison to the control animals. Co-treatment with GA improved all these alterations. Taken together, GA could protect the heart against D-GAL-induced aging via antioxidant effects, and the enhancement of SIRT1, PGC-1α, and TFAM genes expression.

Background The nucleus accumbens (NAc) plays a principal role in drug reward. It has been reported that metabotropic glutamate receptors (mGlu receptors) play a key role in the rewarding pathway(s). Previous studies have shown the vast allocation of the different types of mGlu receptors, including mGlu8 receptors, in regions that are associated with opioid rewards, such as the NAc. The aim of the present study was to evaluate the role of mGlu8 receptors within the NAc in the acquisition and expression phases of morphine induced conditioned place preference (CPP). Adult male Wistar rats were bilaterally implanted by two cannulas' in the NAc and were evaluated in a CPP paradigm. Selective mGlu8 receptor allosteric agonist (S-3,4-DCPG) was administered at doses of 0.03, 0.3, and 3 μg/0.5 μL saline per side into the NAc on both sides during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase, or before place preference test, or post-conditioning (expression) phase of morphine-induced CPP. Results The results revealed that intra-accumbal administration of S-3,4-DCPG (0.3 and 3 μg) markedly decreased the acquisition in a dose-dependent manner but had no effect on expression of morphine-induced CPP. Conclusions The findings suggest that activation of mGlu8 receptors in the NAc dose-dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine which may be related to the glutamate activity into the NAc and in reward pathway(s). These data suggest that mGlu8 receptor may be involved in conditioned morphine reward.

Background and Objectives: Kaempferol (KM) is one of the most important plants with neuroprotection and analgesic effects. In addition, bicuculline (BIC) is a competitive antagonist of the GABAA ionotropic receptor (the most important targets of benzodiazepines and other anxiety suppressants). In this study, intracerebroventricular microinjection of KM on anxiety and its interaction with GABAergic mechanism were investigated in male rats. Materials and Methods: In this exploratory investigation, the male rats were divided into the following groups: control (saline), groups treated by KM (0.5 and 2 mg/rat), DMSO (1mg/rat), KM 0.5+BIC1 mg/rat, KM 0.5+BIC4 mg/rat, KM 2+BIC1 mg/rat, BIC groups (1, 4 mg/rat), and KM 2+BIC 4 mg/rat. Besides, an elevated plus-maze paradigm was used for the evaluation of the anxiety. Results: Statistical analysis revealed that the indices of TTOA in KM groups (0.5 and 2 mg/rat) significantly increased in comparison to the control group (P

In addition to its anticonvulsant effect, low frequency stimulation (LFS) improves learning and memory in kindled animals. In the present study, the role of 5-HT 1A receptors in mediating LFS’ improving effect on spatial learning and memory was investigated in amygdala-kindled rats. Amygdala kindling was conducted in a semi-rapid kindling stimulations (12 stimulations per day) in male Wistar rats. LFS (4 trains of 0.1 ms pulse duration at 1 Hz, 200 pulses, 50–150 μA, at 5 min intervals) was applied after termination of kindling stimulations. NAD-299 (a selective 5-HT 1A receptor antagonist; 2.5 and 5 μg/μl) was microinjected into the hippocampal CA1 before applying LFS. The Morris water maze, and novel object recognition tests were conducted after the last kindling stimulation. Hippocampal samples were also prepared, and 5-HT 1A receptor gene expression levels were assessed using quantitative RT-PCR. In kindled animals, LFS reduced impairments in spatial learning and memory in the Morris water maze and novel object recognition tests. Microinjection of NAD doses of 5 μg/μl reduced the effects of LFS on learning and memory. The gene expression level of 5-HT 1A receptors increased significantly in the hippocampus of amygdala-kindled rats. However, LFS applied after kindling stimulations inhibited this effect. It seems that activation of 5-HT 1A receptors in the CA1 field is necessary for LFS’ improving effects on spatial learning and memory in kindled animals; although surprisingly, LFS application prevented the elevation in gene expression of 5-HT 1A receptors in kindled animals. © 2019 Elsevier Inc.

Increased vulnerability to drug abuse has been observed after exposure to stress and the prefrontal cortex (PFC) plays a major role in the control of the stress response and reward pathway. The current study was conducted to clarify the effects of acute and chronic restraint stress on PFC neural activity during the reinstatement of methamphetamine (METH)-induced conditioned place preference (CPP) in rats. Following the establishment of CPP (METH 0.5 mg/kg; s.c. for 3 days) and the extinction phase, male Wistar rats were divided into threshold (0.25 mg/kg; s.c.) and sub-threshold (0.125 mg/kg; s.c.) METH-treated super groups to induce reinstatement. Each super group contained control (non-stressed), acute restraint stress (ARS) and chronic restraint stress (CRS) groups. in vivo single unit recordings were performed on the urethane-anesthetized rats in these groups. After baseline recordings (10-min period) of the neurons in the PFC, their firing activity was recorded for 50 min during the reinstatement phase after injection of METH. The results showed that the threshold dose, but not the sub-threshold dose, of METH significantly increased PFC neural activity in the non-stressed animals. The sub-threshold dose of METH notably changed this activity in both the ARS and CRS groups. These changes in the excited neurons after the sub-threshold dose in the ARS and CRS groups were significantly higher than those in the non-stressed group. It appears that the PFC is implicated in the associated reward pathway and stress functions. METH affected the firing rate of PFC neurons and stress amplified the effect of METH on changes in the neuronal firing rate in the PFC.

Background: Nowadays, anesthetic drugs are widely used in anesthesia and surgical procedures and their effects on memory have been the focus of attention for a very long time. The effects of these common drugs include Dexmedetomidine (DEX) and Etomidate (ETO), on memory are controversial. In this study, the effects of these two drugs, co-administrated with heights stress, were evaluated on short-term and long-term spatial memory. 48 male mice were divided into 6 experimental groups consisting of Control, Control+heightstress (H.S), ETO, ETO+H.S, DEX+H.S. Drugs were administered Intra-peritoneal with doses of 0.3-0.4 mg/kg and 11 mg/kg for DEX and ETO respectively, and spatial memory was assessed using the Barnes Model.Results: DEX improved acquisition and retention of spatial reference memory, whereas ETO showed no such effects. In addition, DEX and ETO showed excitatory effects on short-term spatial memory, however DEX was more effective than ETO.Conclusion: the results suggested the neuoprotective, synaptic plasticity and memory improving effects of DEX on spatial reference and working memory. However, the precise neuronal and molecular mechanisms of these effects and their relation to the anti-stress system is still unknown and requires further research.

The entorhinal cortex (EC) plays a pivotal role in epileptogenesis and seizures. EC expresses high density of serotonergic receptors, especially 5-HT

Background Several studies have shown that glutamate neurotransmission in the nucleus accumbens (NAc) is required for the development of morphine-induced conditional place preference (CPP). In addition, metabotropic glutamate receptors (mGluRs) in NAc play important roles in the reward pathways. However, the precise role of mGluR4 in different steps of the morphine-induced CPP is less well known. In the present study the effect of bilateral intra-accumbal infusion of VU0155041, as a specific mGluR4 agonist on the acquisition and expression of morphine induced CPP in male Wistar rats was investigated. The animals were bilaterally implanted with guide cannulae above the NAc. In the first step of the study, the VU0155041 was administered at doses of 10, 30 and 50 μg/0.5 μL saline per side into the NAc during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase of morphine-induced CPP. In the second step of the study, the rats bilaterally received VU0155041 at the dose of 50 μg/0.5 μL, 5 min before the post-conditioning test in order to check the effect of VU0155041 on the expression of morphine-induced CPP. Results The results showed that the intra-accumbal injection of VU0155041 inhibits the acquisition of morphine-induced CPP in a dose dependent manner, but had no effect on expression. Conclusions The data indicated that intra-NAc administration of VU0155041 dose dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine. These effects may be related to changes in glutamate activity in the NAC and/or learning dependent mechanism of glutamate neurotransmission in reward pathway(s).

Background: Several studies have shown that glutamate neurotransmission in the nucleus accumbens (NAc) is required for the development of morphine-induced conditional place preference (CPP). Also, metabotropic glutamate receptors (mGluRs) into the NAc play important roles in the reward pathways. However, the precise role of mGluR4 in different steps of the morphine-induced CPP is less well known. In the present study we investigated the effect of bilateral intra-accumbal infusion of VU0155041, as a specific mGluR4 agonist on the acquisition and expression of morphine induced CPP in male Wistar rats. Animals were bilaterally implanted with guide cannulae above the NAc. In the first part of the study, the VU0155041 was administered at doses of 10, 30 and 50 μg/0.5 μL saline per side into the NAc during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase of morphine-induced CPP. In the next part of the study, the rats bilaterally received VU0155041 at the dose of 50 μg/0.5 μL, 5 min before the post-conditioning test to check the effect of VU0155041 on the expression of morphine-induced CPP. Results: The results showed that the intra-accumbal injection of VU0155041 inhibits the acquisition of morphine-induced CPP in a dose dependent manner, but had no effect on expression Our data indicated that intra-NAc administration of VU0155041 dose-dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine.These effects may be related to changes in glutamate activity in the NAC and/or learning dependent mechanism of glutamate neurotransmission in reward pathway(s).

BackgroundThe nucleus accumbens (NAc) plays a principal role in drug reward. It has been reported that metabotropic glutamate receptors (mGluRs) play a key role in the rewarding pathway(s). Previous studies have shown the vast allocation of the different types of mGluRs, including mGluR8, in regions that are associated with opioid rewards, such as the NAc. The aim of the present study was to evaluate the role of mGlu8 receptors within the NAc in the acquisition and expression phases of morphine induced conditioned place preference (CPP). Adult male Wistar rats were bilaterally implanted by two cannulas' in the NAc and were evaluated in a CPP paradigm. Selective mGluR8 allosteric agonist (S-3,4-DCPG) was administered at doses of 0.03, 0.3, and 3μg/0.5 μL saline per side into the NAc on both sides during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase, or before place preference test, or post-conditioning (expression) phase of morphine-induced CPP. ResultsThe results revealed that intra-accumbal administration of S-3,4-DCPG (0.3 and 3 μg) markedly decreased the acquisition in a dose-dependent manner but had no effect on expression of morphine-induced CPP. ConclusionsThe findings suggest that activation of mGlu8 receptors in the NAc dose-dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine which may be related to the glutamate activity into the NAc and/or synaptic plasticity of this system in reward pathway(s).

Low frequency stimulation (LFS) has been proposed as a method in the treatment of epilepsy, but its anticonvulsant mechanism is still unknown. In the current study, the hippocampal CA1 region was microinjected with NAD-299 (a selective 5-HT1A antagonist), and its role in mediating the inhibitory action of LFS on amygdala kindling was investigated. Male Wistar rats were kindled by amygdala stimulation in a semi-rapid kindling manner (12 stimulations per day). LFS (0.1 ms pulse duration at 1 Hz, 200 pulses, 50–150 μA) was applied at 5 min after termination of daily kindling stimulations. NAD (a selective 5-HT1A antagonist) was microinjected into the CA1 region of the hippocampus at the doses of 2.5 and 5 μg/1 μl. An open field test was also run to determine the motor activity of animals in different experimental groups. The application of LFS following daily kindling stimulations reduced the behavioral seizure stages, afterdischarge duration, and stage 5 seizure duration and increased the latency to stage 4 seizure compared to the kindled group. However, microinjection of NAD at the doses of 5 μg/1 μl, but not 2.5 μg/1 μl, blocked the inhibitory effect of LFS on behavioral and electrophysiological parameters in kindled animals. It could be presumed that 5-HT1A receptors in the CA1 area are involved in mediating the antiepileptic effects of LFS.

Previous studies indicate that metabotropic glutamate receptor type 2/3 (mGluR2/3) has a key role in the rewarding properties of morphine-induced conditioning place preference (CPP). Group II mGluR2/3 agonists are offered as a drug addiction treatment. The nucleus accumbens (NAc), which is one of the important areas involved in the reward circuitry, also expresses these receptors. In this study, we evaluated the effects of mGluR2/3 agonist, LY379268, on the extinction and reinstatement of morphine-induced CPP, following its microinjection into the NAc. Adult male Wistar rats (220-250 g) were implanted bilaterally by two separate cannulae into the NAc. After the acquisition of morphine CPP, different doses of LY379268 (0.3, 1 and 3 µg/0.5 μl saline) were microinjected into the NAc every day during the extinction period and, in a different set of experiments, on the reinstatement test day, 60 min before the infusion of a priming dose of morphine (1 mg/kg; subcutaneous). Thereafter, the animals were tested for place preference by the Ethovision software. The intra-accumbal injection of the mGluR2/3 agonist, LY379268, significantly decreased the extinction latencies and reinstatement of morphine-induced CPP at higher doses. It seems that the NAc might be a functional region for mGluR2/3 to play a regulatory role for decreasing drug-seeking behavior in rats. Furthermore, it can be said that mGluR2/3 agonists have a potential role in the treatment of drug-seeking behaviors.

Introduction Administration of low-frequency electrical stimulation (LFS) at the kindling site has an antiepileptogenic effect. In the present study, we investigated the role of cannabinoid receptors type 1 (CB1) in mediating the inhibitory effects of LFS on the development of perforant path kindled seizures. Methods For seizure generation, rats were kindled by electrical stimulation of perforant path in semi-rapid kindling manner (12 stimulations per day at 10 min intervals at afterdischarge threshold intensity).To determine the effect of LFS (0.1 ms pulse duration at 1 Hz, 800 pulses) on seizure generation, LFS was applied to the perforant path 5 min after the last kindling stimulation daily. AM281, a CB1 receptor antagonist, was microinjected into the lateral ventricle immediately after the last kindling stimulation (before LFS application) at the doses of 0.5 and 2 μg/μl during kindling procedure. The expression of cannabinoid receptors in the dentate gyrus was also investigated using immunohistochemistry. Results Application of LFS had inhibitory effect on development of kindled seizures (kindling rate). Microinjection of AM281 (0.5 μg/μl) immediately after the last kindling stimulation (before LFS application) reduced the inhibitory effect of LFS on the kindling rate and suppressed the effects of LFS on potentiation (increasing the magnitude) of both population spike amplitude and population excitatory postsynaptic potential slope during kindling acquisition. AM281 pretreatment also prevented the effects of LFS on kindling-induced increase in early and late paired pulse depression. The higher dose of AM281 (2 μg/μl) failed to exert the effects observed with its lower dose (0.5 μg/μl). In addition, there was a decreased CB1 receptors immunostaining in kindled animals compared to control. However, application of LFS following kindling stimulations led to overexpression of CB1 receptors in the dentate gyrus. Conclusion Obtained results showed that activation of overexpressed cannabinoid CB1 receptors by endogenous cannabinoids may have a role in mediating the inhibitory effect of LFS on perforant path kindled seizures.

The neurotransmitter γ-aminobutyric acid (GABA) is involved in the process of memory. It has been reported that the inhibition of GABAB receptors has beneficial effects on cognition. The aim of this study was to investigate the role of CGP35348 (a GABAB receptor antagonist) on dentate gyrus GABAB receptor inhibition and its effects on learning and memory impairments that had been induced in adult male rats by microinjection of β-amyloid (Aβ). Seventy Wistar male rats were randomly divided into seven groups: control, sham (receiving the Aβ vehicle only), Aβ, Aβ + CGP35348 (1, 10, and 100 μg/μL), and CGP35348 alone (10 μg/μL). Memory impairment was induced by unilateral interventricular microinjection of Aβ (6 μg/6 μL). Rats were cannulated bilaterally in the dentate gyrus, and then, they were treated for 20 consecutive days. Learning and memory were assessed using the novel object recognition and passive avoidance learning tests. The discrimination index and the step-through latency were significantly increased in the Aβ + CGP35348 group in comparison to the Aβ only group (P

Introduction The signaling pathways involved in the antiepileptogenic effect of low frequency electrical stimulation (LFS) have not been fully understood. In the present study the role of extracellular signal-regulated kinase (ERK) signaling cascade was investigated in mediating the inhibitory effects of LFS on kindled seizures. Methods Animals received kindling stimulations for seven days (the mean number of stimulation days for achieving stage 5 seizure) according to semi-rapid perforant path kindling protocol (12 stimulations per day at 10 min intervals). LFS (0.1 ms pulse duration at 1 Hz, 800 pulses) was applied at 5 min after the last kindling stimulation every day. During the kindling procedure, FR180204 (inhibitor of ERK) was daily microinjected (1 μg/μl; intracerebroventricular) immediately after the last kindling stimulation and before LFS application. The expression of activated ERK (p-ERK) in the dentate gyrus was also investigated using immunohistochemistry technique. Results Application of LFS at 5 min after the last kindling stimulation had inhibitory effect on kindling rate. FR180204 had no significant effect on seizure parameters when administered at the dose of 1 μg/μl in kindled group of animals. However, microinjection of FR180204 before LFS application reduced the inhibitory effect of LFS on seizure severity and field potential parameters (i.e. the slope of population field excitatory postsynaptic potentials and population spike amplitude) during kindling. FR180204 also blocked the preventing effects of LFS on kindling-induced increase in early (at 10–40 ms intervals) and late (at 300–1000 ms intervals) paired pulse depression. In addition, application of LFS following kindling stimulations increased the expression of p-ERK in the dentate gyrus. Conclusion Obtained results showed ERK signaling pathway had important role in mediating the antiepileptogenic effect of LFS in perforant path kindling. These findings represent a promising opportunity to gain insight about LFS mechanism in epilepsy therapy.

Obesity and a high-fat diet (HFD) are known to increase the incidence of Alzheimer’s disease (AD). Oxidative stress, a major risk factor for AD, is increased with HFD consumption. Thymol (Thy) has antioxidant properties. Therefore, in the present study, we examined the protective and therapeutic effects of Thy on amyloid-β (Aβ)-induced impairments in the hippocampal synaptic plasticity of HFD-fed rats. In this study, 72 adult male Wistar rats were randomly assigned to 9 groups (n = 8 rats/group): Group 1 (control; standard diet); Group 2: Control + phosphate-buffered saline (PBS) + Oil (Thy vehicle); Group 3 (HFD + PBS); Group 4: (HFD + Aβ); Group 5: Control + PBS + Thy; Group 6: (HFD + Aβ + Oil); Group 7: Control + Aβ + Thy; Group 8: HFD + PBS + Thy; Group 9: (HFD + Aβ + Thy). After stereotaxic surgery, the field potentials were recorded after the implantation of the recording and stimulating electrodes in the dentate gyrus (DG) and perforant pathway, respectively. Following high-frequency stimulation, the long-term potentiation (LTP) of the population spike (PS) amplitude and the slope of the excitatory postsynaptic potentials (EPSPs) were measured in the DG. The HFD rats that received Aβ exhibited a significant decrease in their EPSP slope and PS amplitude as compared to the control group. In contrast, Thy administration in the HFD + Aβ rats reduced the decrease in the EPSP slope and PS amplitude. Thy decreased the Aβ-induced LTP impairments in HFD rats. The HFD significantly increased serum malondialdehyde levels and decreased total antioxidant capacity and total glutathione levels; whereas, Thy supplementation significantly reversed these parameters. Therefore, these results suggest that Thy, a natural antioxidant, can be therapeutic against high risk factors for AD, such as HFD.

Methamphetamine (Meth) abuse and dependence are major global problems. Most of previous studies showed that Meth is anxiogenic. While buprenorphine (Bup) is used to treat anxiety-related behaviors, the effects of Meth in combination with Bup on anxiety-like behavior are unclear. In this study, we examined the effects of these drugs on anxiety-like behavior with the elevated plus maze (EPM) and open field (OF) tests, which are widely used to assess anxiety-like behavior in small rodents. Forty male Wistar rats were divided into four groups: sham, Meth, Bup, and Bup+Meth. The groups were administered their assigned treatments for 7days. The time spent in the open arms, and number of total entries into the arms (total activity) in the EPM were recorded. In addition, locomotor activity and number of entrances into the center area in the OF were recorded. The 7-day administration of Meth or Bup increased open arm exploration in the EPM. In contrast, the combined administration of Bup and Meth had the opposite effects. In addition, Meth and Bup had no effects on total and locomotor activity. Furthermore, the rats in the Meth and Bup groups spent more time in the center of the OF, while the group given both Bup and Meth spent less time in the center of the OF. The administration of Meth and Bup alone was anxiolytic in rats, whereas the coadministration of Bup and Meth was anxiogenic.

Introduction Recent studies have shown that medial pre-optic area (MPOA) of hypothalamus are involved in nociception. Orexin A (hypocretin 1) has been found to have numerous applications including pain modulation. However, the role of orexin A receptors in the MPOA on the nociception has not been yet studied. Therefore, the aim of the present study is to investigate the effect of orexin A microinjection on MPOA on the nociception transmission and morphine induced analgesia in adult male rats. Methods Using stereotaxic surgery, a cannula was implanted at a site 1 mm above the MPOA in the anesthetized rats. After the recovery period, tail-flick (TF) latency was measured as 0, 15, 30, 45 and 60 min following the onset of two experimental protocols. Two experiments were carried out. Experiment 1: The male rats received intra-MPOA of 25, 100, 1000, 10000 pmol/0.5 μl orexin A or 0.5 μl of aCSF (control, just 5 min before the TF assay. Experiment 2: The aim of this experiment was to examine the effect of orexin microinjection into MPOA on morphine analgesia (3 mg/kg, s.c). Morphine was administered 30 min before orexin A intra-MPOA microinjection (four doses similar to experiment 1) or aCSF, then TF latency was measured. Results The results indicated that microinjection of orexin A into the MPOA showed anti-nociceptive effect in a time-dependent manner. Dose response curve results also revealed that the maximum effective dose of orexin A injection into MPOA for pain inhibition is 1000 pmol/0.5 μl. Co-administration of systemic morphine and orexin into the MPOA has additive analgesia with different time course compared morphine or orexin alone. Conclusion It can be concluded that MPOA OrexinA receptors play an important role in the modulation of pain in normal and morphine treated male rats.

Long-term potentiation (LTP) of synaptic transmission is a cellular process underlying learning and memory. Cannabinoids are known to be powerful modulators of this kind of synaptic plasticity. Changes in GABAergic inhibition have also been shown to affect synaptic plasticity in the hippocampus. GABA receptor type B (GABAB) and cannabinoid receptor type 1 (CB1) exhibit overlapping anatomical localization in some brain areas including the hippocampus. CB1 and GABAB are also localized to the same cells and share a common signaling pathway in some brain areas. In this study, we examined the hippocampal effects of co-administrating AM251 and CGP55845, which are CB1 and GABAB antagonists, respectively, on LTP induction in the dentate gyrus (DG) of rats. LTP in the hippocampal area was induced by high-frequency stimulation (HFS) of the perforant path. Our results showed that HFS coupled with administration of the CB1 antagonist increased both the population spike (PS) amplitude and field excitatory post-synaptic potential (fEPSP). Conversely, the GABAB antagonist decreased these parameters along with decreased LTP induction. We also demonstrated that the co-administration of CB1 and GABAB antagonists had different effects on the PS amplitude and fEPSP slope. It is likely that GABAB receptor antagonists modulate cannabinoid outputs that cause a decrease in synaptic plastisity, while in the simultaneous consumption of two antagonists, CB1 antagonists can alter the release of GABA which in turn results in enhancement of LTP induction. These findings suggest that there are functional interactions between the CB1 and GABAB receptor in the hippocampus.

Alzheimer’s disease (AD) is a neurodegenerative disease leading to cognitive and memory impairment. This study aimed at investigating the therapeutic and preserving effects of vinpocetine on amyloid beta (Aβ)-induced rat model of AD. Sixty male adult Wistar rats were randomly divided into 6 groups (n = 10 per group) as follows: 1; control, 2; sham, 3; Aβ, 4; pre-treatment (vinpocetine + Aβ): oral gavage administration of vinpocetine at 4 mg/kg for 30 days followed by intracerebroventricular (ICV) injection of Aβ, 5; treatment (Aβ + vinpocetine): Aβ ICV injection followed by vinpocetine administration for 30 days, 6; pre-treatment + treatment (vinpocetine + Aβ + vinpocetine): vinpocetine administration for 30 days before and 30 days after AD induction. Following treatments, the animals’ learning and memory were investigated using passive avoidance learning (PAL) task, Morris water maze (MWM), and novel object recognition (NOR) tests. The results demonstrated that Aβ significantly enhanced escape latency and the distance traveled in the MWM, decreased step-through latency, and increased time spent in the dark compartment in PAL. Vinpocetine ameliorated the Aβ-infused memory deficits in both MWM and PAL tests. Administration of vinpocetine in the Aβ rats increased the discrimination index of the NOR test. It also significantly diminished the nitric oxide and malondialdehyde levels and restored the reduced glutathione (GSH) levels. Vinpocetine can improve memory and learning impairment following Aβ infusion due to its different properties, including antioxidant effects, which indicates that vinpocetine administration can lead to the amelioration of cognitive dysfunction in AD.

Background Learning and memory are among the most important cognitive functions of the brain. Melatonin receptor type 2 (MT2R) is located in the hippocampus and participates in learning and memory processes. In the present study, we examined the role of hippocampal MT2R activation in the acquisition, consolidation, and retrieval of learning and memory in novel object recognition (NOR) and passive avoidance (PA) tasks. Methods IIK7 (0.03, 0.3, and 3 μg/μl/side), as a selective MT2R agonist, or vehicle was injected bilaterally into the dentate gyrus (DG) region of the hippocampus in rats five minutes before training, immediately after training, and five minutes before the retrieval-behavioral tasks, respectively. The discrimination index (DI) was measured in the NOR task, while step-through latency in acquisition (STLa), number of trials to acquisition (NOT), step-through latency in the retention trial (STLr), and time spent in the dark compartment (TDC) were determined in the PA task. Results The pretraining intrahippocampal injection of IIK7 at all doses significantly improved acquisition in the PA task. On the other hand, the posttraining intrahippocampal administration of IIK7 had no significant effects on consolidation. The preretrieval intrahippocampal injection of IIK7 at different doses attenuated the retrieval of memory. However, the NOR data showed that the intrahippocampal injection of IIK7 at different doses had no significant effects on the acquisition, consolidation, or retrieval in this task. Discussion Based on the findings, stimulation of MT2R could improve acquisition, whereas it had no effects on consolidation. It could impair retrieval in the PA task, while it had no effects on object recognition in rats.

In addition to its anticonvulsant effect, low frequency stimulation (LFS) improves learning and memory in kindled animals. In the present study, the role of 5-HT

Introduction Methamphetamine (METH) is a neurotoxic psychostimulant with highly addictive potential that leads to compulsive drug use and vulnerability to relapse. Environmental cues, such as drug exposure, peer influence, and social stress, are the powerful triggers of drug relapse. In this study, we tried to find out the effect of acute and chronic restraint stress on reinstatement of extinguished METH-induced Conditioned Place Preference (CPP) in rats. Methods Subcutaneous (SC) administration of METH (0.125, 0.25, 0.5, 1, 2 and 4 mg/kg) could induce CPP and it was found that METH with the dose of 0.5 mg/kg was more potent than other doses. In extinction phase, rats were put in the CPP box for 30 min per day for 8 consecutive days. After extinction, animals were exposed to restraint stress (3-h period, as an acute stress) 60 min before subcutaneous administration of ineffective dose of METH (0.125 mg/kg) in order to reinstate the extinguished METH-induced CPP. For induction of the chronic stress during extinction phase, the animals were exposed to the restraint stress for one hour per day. Results The results showed that the effective dose of METH to induce CPP was 0.5 mg/kg. Based on the results, physical stress (restraint stress) whether acute and chronic, can significantly induce reinstatement of METH-induced CPP (P˂0.001) in extinguished animals. Conclusion Additionally, the chronic restraint stress could reduce duration of extinction (maintenance) of METH-induced CPP. It seems that exposure to the stress induces the relapse in abstinent amphetamine, but acute and chronic situation have a different reaction.