سید ارشاد ندایی

Experience of separation from mother can cause lasting changes in brain structure. Meanwhile, exposure to opioids in adolescence can affect cognitive abilities. In this study, effects of maternal deprivation stress and exposure to morphine in adolescence on anxiety-like behaviors and working memory were evaluated in adult rats.

Male and female Wistar rats including control, maternal deprivation stress (Str), receiving morphine (Morphine) in adolescent, and Morphine with Stress (Mor + Str) group were selected. In the Str group, the offspring was separated from their mothers 3 hours/day for 14 days. Morphine group received increasing doses of morphine from 2.5 to 25 mg/kg for 10 days (31-40 postnatal day). Open field test, elevated plus maze and Y maze were used to investigate locomotor activity, anxiety-like behaviors and working memory of animals, respectively.

There was no significant difference in locomotor activity between morphine and control groups. Morphine group in both sexes spent more time in center of the open field compared to control group, and unlike the Mor + Str group, had stable anti-anxiety behavioral effects until adulthood. Working memory was impaired in both Morphine and Mor + Str groups in both sexes compared to control group.

Maternal deprivation and substance abuse have lasting effects on occurrence of anxiety-like behaviors during the developmental period of adolescence. Maturation of the nervous system can be affected by these adverse environmental factors and underwent permanent behavioral changes and cognitive disorders.

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.

Crocin is one of the main components of saffron. The effect of saffron on birth abortion has been established. So, the possible effect of crocin on abortion was evaluated in this study. Pregnant mice were divided into 8 groups. Each group received crocin (0 or 10 or 50 or 100 mg/kg, i.p.) from the first to the fifth day of pregnancy. Then, the first four groups were sacrificed on the seventh day to evaluate the implantation sites. The other four groups were sacrificed on the 20th day and the number of embryos was counted. Data were analyzed by ANOVA. Administration of crocin (50 and 100 mg/kg) significantly reduced the mean number of implantation sites and embryos compared to the control group (P<0.05). Administration of high doses of crocin in the first week of pregnancy reduced the number of implantation places and embryos in mice.

The cholinergic system plays an important role in learning and memory. Administration of Crocus Sativus (Saffron) or its constituent, Crocin, facilitates the formation of memory. Based on above findings, in the current study the effect of Crocin in antagonizing retrograde amnesia induced by scopolamine, a cholinergic receptor antagonist, in rats was investigated by using shuttle box apparatus.

Male Wistar rats (200 – 250 g) were tested for measuring their learning behavior in a step-through type passive avoidance task. All animals were trained by using a 1 m foot shock. The drugs were injected after the successful training. Animals were tested 24h after training to measure step-through latency (STL).

Post-training injection of scopolamine (1 mg/kg) impaired memory performance on the test day. Moreover, administration of Crocin (1, 5 or 10 mg/kg) 30 min after scopolamine improved scopolamine retrograde amnesia in a dose dependent manner. On the other hand, post-training injection of Crocin (1, 5 or 10 mg/kg) had no any significant effect on passive avoidance memory by itself.

Considering the therapeutic effect of post-training injection of Crocin on scopolamine retrograde amnesia, it may be concluded that Crocin has an interaction with cholinergic system in formation of passive avoidance memory in male rats.

Cyclooxygenase (COX) enzyme known as a regulatory factor in synaptic plasticity. It has been reported that synaptic plasticity is one of the mechanisms involved in learning and memory processes. In the current study peripheral injection's effects of sodium salicylate (as a non selective COX inhibitor) on spatial learning and memory have been investigated. Four groups of male rats received different doses of sodium salicylate (0, 200, 300, 400 mg/kg; i.p.). Studies were performed using Morris Water Maze (MWM). Spatial learning and memory parameters were subjected to the one- and two-way analyses of variance (ANOVAs) followed by Tukey’s post hoc test. Data showed that intraperitoneal injection of sodium salicylate had not significant effect on spatial learning parameters (including escape latency and traveled distance to hidden platform in training days); but administration of high dose of the drug (400 mg/kg) significantly increased the percentage of time that animals spent in the target quadrant in probe trial testing. Peripheral injection of the COX inhibitor has no significant effect on spatial learning; but potentiates spatial memory consolidation using MWM.

Diabetes mellitus is one of the most important diseases in all over the world. Insulin and its receptor are found in specific area of CNS with a variety of regions-specific functions different from its role in direct glucose regulation in the periphery. The hippocampus and cerebral cortex distributed insulin and insulin receptor has been shown to be involved in brain cognitive functions. Previous studies about the effect of insulin on memory in diabetes are controversial and further investigation is necessary. Seventy male NMRI rats (250-300 g) were randomly divided into control, diabetic, saline-saline, saline-insulin (12, 18 or 24 mU), diabetic-saline, diabetic-insulin (12, 18 or 24 mU) groups. Diabetes was induced by streptozotocin (65 mg/kg, ip). Saline or insulin were injected bilaterally (1 µl/rat) into CA1 region of hippocampus during 1 min. Thirty minutes later, water maze training was performed. Insulin had a dose dependent effect. The spatial learning and memory were impaired with diabetes, and improved by insulin. Escape latency and swimming distance in a water maze in insulin treated animals were significantly lower.

Pioglitazone from thiazolidinediones generation, represent a new antidiabetic drugs that have been introduced in the world recently. Thiazolidinediones can improve insulin resistance by activating the nuclear peroxoxisome proliferator activated receptor-γ (PPAR-γ) and increasing insulin sensitivity in their receptors. Insulin and its receptors are found in specific areas of CNS with a variety of region-specific functions. The effects of insulin in CNS are different from its direct glucose regulation in the periphery. Hippocampus and cerebral cortex distributed insulin/insulin receptor have been shown to be involved in brain cognitive functions. In the present study, the effect of pioglitazone microinjection into CA1 region of rat hippocampus using Morris water maze performance has been investigated. In this experimental study, male N-MRI rats were randomly divided into control, DMF (dimethyl formamide) and pioglitazone groups (0.001, 0.01, 0.1, 1, 10 µg/rat). Drugs were injected (1 µl/rat) into CA1 region bilaterly during 1 min. Thirty minutes after the intrahippocampal injection of drugs, water maze training was started. Pioglitazone had a dose dependent effect. The spatial learning and memory didn’t change with lower dose of pioglitazone, but improved with intermediate doses, while they impaired with higher dose. These results suggest that intrahippocampal injection of pioglitazone may have a dose-dependent effect on spatial learning and memory in rats in range of 0.001 to 1 µg/rat.

N-methyl-D-aspartate (NMDA) receptors play a pivotal role in the development of tolerance and physical dependence to opiates. Activation of NMDA receptors involves the induction of long term potentiation (LTP) in hippocampus. Our previous study suggested that chronic oral administration of morphine enhanced NMDA dependent LTP in the CA1 area of hippocampal slices of rats. The present study examines the expression levels of individual NMDA receptor subunits, NR1, NR2A and NR2B, in the hippocampus of morphine-dependent rats by using western blotting. Total proteins of hippocampus were extracted by Tris-HCl buffer containing anti proteases and sodium dodecyl sulfate (SDS). The extracted proteins were resolved by SDS-PAGE and transferred to polyvinylidenefloride (PVDF) membrane by tank blotting and the subunits of NMDA receptor were analyzed by immunoblotting by using specific antibodies. Obtained results provide both biochemical and statistical evidence to suggest that NMDA receptor function in the hippocampus, at least in terms of expression of NR1, NR2A and NR2B protein subunits, increases in morphinedependent rats. Taken together, these data support several studies in the literature indicating that NMDA receptors in the hippocampus are involved in the process of opiate dependence.

The N-methyl-D-aspartate (NMDA) receptors, which have been implicated in memory formation, could be noncompetitively blocked by ketamine. The present study examines the short term effect of ketamine on induction of anterograde and retrograde amnesia in male rats using Morris water maze (MWM). Male N-MRI rats were randomly divided into nine experimental groups. MWM studies were performed to evaluate spatial learning and memory parameters. In order to examine the effect of ketamine on the induction of anterograde amnesia, 4 groups of animals received daily injections of ketamine (1, 3, 6 or 12 mg/kg, i.p.) 10 min before testing on training days. To examine the effect of drug on the induction of retrograde amnesia four other groups of rats received daily injection of normal saline (on training days) and ketamine (1, 3, 6, or 12 mg/kg, i.p.) (in probe trial) 10 min before testing. Rats of the control group received normal saline on all days of experiments. Spatial learning and memory parameters were recorded and subjected to the analysis of variance (ANOVA). Difference was considered significant if p<0.05. Data showed that injection of ketamine at the dose of 3 mg/kg and higher inhibits spatial learning and memory parameters and induces both anterograde and retrograde amnesia in rats. It seems that ketamine induces inhibitory effects on spatial learning and memory via blocking the NMDA receptors. On the other hand, ketamine induced dose dependent decrease in swim speed which was significant at the dose of 12 mg/kg.