Basic and Clinical Neuroscience
Volume:6 Issue: 3, Summer 2015

Previous studies have shown that cannabinoidergic system is involved in anxiety. However, there are controversial reports in the experimental studies. The aim of this study is to evaluate the effect of pharmacological stimulation or blocking of CB1 receptors and inhibition of endocannabinoid degradation in anxiety like behavior in elevated plus-maze (EPM) test in rat. The EPM is one of the most widely used animal models of anxiety. Male Wistar rats were randomly allocated to ten groups. Different groups of animals intraperitoneally received Win-55212 (0.3, 1 and 5 mg/kg) as CB1 receptor agonist, AM- 251 (0.3, 1 and 5 mg/kg) as CB1 receptor antagonist, URB-597 (0.03, 0.1 and 0.3 mg/kg) as endocannabinoid breakdown inhibitor or saline (as control group) 30 min before submitting into EPM test. The results showed that compared to the control group, Win-55212 (1 and 5 mg/kg) and URB-597 (0.1 and 0.3 mg/kg) significantly increased both of the time and percentage of entries into open arms. AM-251 (1 and 5 mg/kg) significantly decreased the time and percentage of entries into open arms in the EPM test. These substances have no effects on the total distance covered by animals and number of closed arm entries. It is concluded that activation of cannabinoid receptor exert anxiolytic effect while blocking of cannabinoid receptor resulted in anxiety behavior. The locomotor activity was not significantly changed by cannabinoid system. It is suggested that potentiation of cannabinoid system may be therapeutic strategy for the anxiety behavior.

Recent studies suggest that glucocorticoids modulate memory reconsolidation. Moreover, cholinergic system is involved in memory reconsolidation. Since glucocorticoids interact with brain cholinergic system in modulating memory processing, we investigated whether glucocorticoid influences on the reconsolidation of emotionally arousing training depend on the cholinergic system. Mice were trained (1mA, 3s footshock) in an inhibitory avoidance task. Forty-eight hours after training, memory reactivation was occurred (Test 1), and different treatments were given. Two (Test 2), five (Test 3), and seven days (Test 4) after memory reactivation (Test 1), animals were retested for fear memory retention. In the first experiment, we observed that administration of corticosterone (CORT, 0.3, 1 and 3 mg/kg) following memory reactivation impaired subsequent expression of memory in a dose-dependent manner. In the second experiment, we found that CORT-induced impairment of memory reconsolidation was reversed by the muscarinic receptor antagonist atropine (0.5 and 2 mg/kg). In the third experiment, the nicotinic receptor antagonist mecaylamine (0.5 or 2 mg/kg) was not able to block the corticosterone response. These findings indicate that glucocorticoids impair memory reconsolidation by a muscarinic cholinergic mechanism.

The plethora of studies indicated that there is a cross talk relationship between harmaline and serotonergic (5-HT) system on cognitive and non-cognitive behaviors. Thus, the purpose of this study is to assess the effects of hippocampal 5-HT4 receptor on memory acquisition deficit induced by harmaline. Harmaline was injected peritoneally, while 5-HT4 receptor agonist (RS67333) and antagonist (RS23597-190) were injected intra-hippocampal. A single-trial step-down passive avoidance, open field and tail flick tasks were used for measurement of memory, locomotor activity and pain responses, respectively. The data revealed that pre-training injection of higher dose of harmaline (1 mg/kg), RS67333 (0.5 ng/mouse) and RS23597-190 (0.5 ng/mouse) decreased memory acquisition process in the adult mice. Moreover, concurrent pre-training administration of subthreshold dose of RS67333 (0.005 ng/mouse) or RS23597-190 (0.005 ng/mouse) with subthreshold dose of harmaline (0.5 mg/kg, i.p.) intensify impairment of memory acquisition. All above interventions did not change locomotion and tail flick behaviors. The results demonstrated that the synergistic effect between both hippocampal 5-HT4 receptor agonist and antagonist with impairment of memory acquisition induced by harmaline, indicating a modulatory effect for hippocampal 5HT4 receptor on Harmaline induced amnesia.

The neuroprotective role of opioid morphine against 6-hydroxydopamineinduced cell death has been demonstrated. However, the exact mechanism(s) underlying such neuroprotection, especially the role of subtype receptors, has not yet been fully clarified. Here, we investigated the effects of different opioid agonists on 6-OHDA-induced neurotoxicity in human neuroblastoma SH-SY5Y cell line as an in vitro model of Parkinson’s disease. Cell damage was induced by 150 μM 6-OHDA and the cells viability was examined by MTT assay. Intracellular calcium, reactive oxygen species and mitochondrial membrane potential were assessed by fluorescence spectrophotometry method. Immunoblot technique was used to evaluate cytochrome-c and activated caspase-3 as biochemical markers of apoptosis induction. The data showed that 6-OHDA caused significant cell damage, loss of mitochondrial membrane potential and increase in intracellular reactive oxygen species and calcium levels as well as activated caspase-3 and cytochrome-c release. Incubation of SH-SY5Y cells with μ-opioid agonists, morphine and DAMGO, but not with δ-opioid agonist, DADLE, elicited protective effect and reduced biochemical markers of cell damage and death. The results suggest that μ-opioid receptors signaling participate in the opioid neuroprotective effects against 6-OHDA-induced neurotoxicity.

X chromosome inactivation (XCI) is a process during which one of the two X chromosomes in female human is silenced leading to equal gene expression with males who have only one X chromosome. Here we have investigated XCI ratio in females with opioid addiction to see whether XCI skewness in women could be a risk factor for opioid addiction. 30 adult females meeting DSM IV criteria for opioid addiction and 30 control females with no known history of addiction were included in the study. Digested and undigested DNA samples which were extracted from blood were analyzed after amplification of the polymorphic androgen receptor (AR) gene located on the X chromosome. XCI skewness was studied in 3 ranges: 50:50–64:36 (random inactivation), 65:35–80:20 (moderately skewed) and >80:20 (highly skewed). XCI from informative females in control group was 63% (N=19) random, 27% (N=8) moderately skewed and 10% (N=3) highly skewed. Addicted women showed 57%, 23% and 20%, respectively. The distribution and frequency of XCI status in women with opioid addiction was not significantly different from control group (P=0.55). Our data did not approve our hypothesis of increased XCI skewness among women with opioid addiction or unbalanced (non-random) expression of genes associated with X chromosome in female opioid addicted subjects.

Lower level of estrogen hormone is considered as an important factor for loss of learning and memory in postmenopausal women. Although estrogen replacement therapy is used for compensation, but long-term usage of estrogen is associated with a higher risk of hormonedependent cancers. Phytoestrogens, due to fewer side effects, have been proposed to prevent menopause-related cognitive decline. 24 female Wistar rats weighing 180-220 g were used in this study. The animals were ovariectomized and randomly divided into four groups including, control and two groups which received 8 and 80 mg/kg Vitex agnus castus (VAC) ethanolic extract orally. The last groups were treated with 40 μg/kg of estradiol valerat. Step-through passive avoidance (STPA) test was used for the evaluation of learning and memory. The hippocampal estrogen receptor α (ERα) expression was measured using Real-Time PCR. The results demonstrated that VAC extract or estradiol had better performance on stepthrough passive avoidance test than control group (all P<0.05). Moreover, administration of either estradiol or VAC extract increased the hippocampal mRNA level of ERα and prevented the decrease in uterine weight of ovariectomized rats. Based on our data, VAC extract improves learning and memory in ovariectomized rats. The positive effect of VAC extract on learning and memory is possibly associated with an increase in ERα gene expression in the hippocampal formation.

Computer games have attracted remarkable attentions in general publics with different cultures and their effects are subject of research by cognitive neuroscientists. In the present study, possible effects of the game Fifa 2015 on cognitive performance, hormonal levels, and electroencephalographic (EEG) signals were evaluated in young male volunteers. Thirty two subjects aged 20 years on average participated mutually in playing computer game Fifa 2015. Identification information and general knowledge about the game were collected. Saliva samples from the contestants were obtained before and after the competition. Perceptive and cognitive performance including the general cognitive health, response delay, attention maintenance, and mental fatigue were measured using PASAT test. EEG were recorded during the play using EEG device and analyzed later using QEEG. Simultaneously, the players’ behavior were recorded using a video camera. Saliva cortisol levels were assessed by ELISA kit. Data were analyzed by SPSS program. The impact of playing computer games on cortisol concentration of saliva before and after the game showed that the amount of saliva plasma after playing the game has dropped significantly. Also the impact of playing computer games on mental health, before and after the game indicated that the number of correct answers has not changed significantly. This indicates that sustained attention has increased in participants after the game in comparison with before that. Also it is shown that mental fatigue measured by PASAT test, did not changed significantly after the game in comparison to before that. The impact of game on changes in brain waves showed that the subjects in high activity state during playing the game had higher power of the EEG signals in most of the channels in lower frequency bands in compared to normal state. The present study showed that computer games can positively affect the stress system and the perceptual-cognitive system. Even though this impact was not significant in most cases, the changes in cognitive and hormonal test and also in brain waves were visible. Hence, due to the importance of this matter, it is necessary to create control systems in selecting the types of games for playing.