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Previous investigations have revealed the role of GABAergic and serotonergic systems in the modulation of pain behavior. This research aimed to examine the effects of intracerebroventricular (i.c.v.) infusion of GABAA receptor agonist and antagonist as well as citalopram on pain behavior in male mice. For i.c.v. microinjection, a guide cannula was surgically implanted in the left lateral ventricle of male mice. Pain behavior was evaluated using a tail-flick test. Tail flick latency was measured in each experimental group of mice every 15 min (for 60 min). I.c.v. microinjection of muscimol (0.5 and 1 µg/mouse; GABAA receptor agonist) into the left lateral ventricle dose-dependently induced an antinociceptive effect. On the other hand, i.c.v. infusion of bicuculline (1 µg/mouse; GABAA receptor antagonist) induced a hyperalgesia response. Moreover, intraperitoneally (i.p.) administration of citalopram (8 mg/kg) produced an antinociceptive effect. Co-treatment of citalopram (8 mg/kg) along with muscimol (0.25 µg/mouse) or bicuculline (0.25 µg/mouse) potentiated the antinociceptive effect produced by citalopram. We found an additive antinociceptive effect of citalopram and muscimol in male mice. In conclusion, our results suggested an interaction between citalopram and GABAergic agents on the modulation of pain behavior in male mice.

Background: There is evidence that both the GABAergic system and serotonin reuptake inhibitor (SSRI) such as citalopram are involved in the modulation of anxiety and depression processes. In this research, we examined the effects of GABAA receptor agents and citalopram on anxiety- and depression-related behaviors and their interaction in male mice. Methods: For intracerebroventricular (i.c.v.) infusion, a guide cannula was implanted in the left lateral ventricle. Anxiety and depression behaviors were evaluated using the elevated plus-maze (EPM) and forced swimming test (FST). Results: The results revealed that i.c.v. microinjection of muscimol (1 µg/mouse) enhanced % OAT (open arm time) and % OAE (open arm entries) in the EPM test and decreased immobility time in the FST without affecting locomotor activity, presenting anxiolytic- and antidepressant-like behaviors in the EPM and FST, respectively. On the other hand, i.c.v. microinjection of bicuculline (1 µg/mouse) reduced % OAT and % OAE without affecting locomotor activity and immobility time, presenting an anxiogenic-like effect. Moreover, i.p. administration of citalopram (8 mg/kg) increased %OAT and %OAE and reduced immobility time with no effect on locomotor activity, showing anxiolytic- and antidepressant-like responses in male mice. Furthermore, i.c.v. infusion of an ineffective dosage of muscimol potentiated the anxiolytic- and antidepressant-like responses induced by i.p. injection of citalopram in male mice. When citalopram and bicuculline were co-injected, a non-significant dose of bicuculline reversed the anxiolytic-like effect of citalopram in male mice. Also, the data revealed synergistic anxiolytic- and antidepressant-like behaviors between citalopram and muscimol in male mice. Conclusions: The results suggested an interaction between citalopram and GABAergic agents on the modulation of anxiety and depression behaviors in male mice.

Background and Aim: The level of Tumor Necrosis Factor-alpha (TNF-α) changes by REM sleep deprivation. TNF-α is a known biomarker of REM sleep deprivation (RSD). Prior studies have shown that any alteration in REM sleep can increase the amount of TNF-α. Accordingly, the Pain Tolerance Threshold (PTT) is believed to be increased in patients with insomnia after using anti-TNF-α or Infliximab (IFX). The present study aims to demonstrate the effect of IFX and its importance in the pain management of hospital inpatients. Methods and Materials/Patients: Seventy-two male Wistar rats in 9 groups were studied after obtaining the approval of the ethics committee of Tehran University of Medical Sciences (CNS.Protocol-ICSS-940816). Remicade was used for inducing the anti-TNF-α. Multiple platform water-tank was used for REM sleep deprivation induction. Pain tolerance was measured on a hot plate apparatus. Results: There was a significant increase in the duration of the rats’ tolerance on the hot plate between the saline group and the group that received IFX (0.2 mg/kg) (F2 = 8.363) (P =

Introduction: Identifying a potent biomarker for smoking cessation can play a key role in predicting prognosis and improving treatment outcomes. This study aimed to evaluate the contribution of new biomarkers based on the levels of Cotinine (Cot) and carbon monoxide (CO) to the short- and long-term quit rates of nicotine replacement therapies (Nicotine Patch [NP] and Nicotine Lozenge [NL]). Methods: In this prospective interventional study, 124 smokers under treatment with the 5A’s method were selected from an outpatient smoking cessation center in district 18 of Tehran City, Iran. The study was conducted from April 2016 to December 2018. They were divided into NP (n=56) and NL (n=61) intervention groups. The levels of Cot and CO were measured using ELISA and breath analysis at the beginning of the study. Three markers were calculated: Cot/CO, Cot to cigarette per day ratio (Cot/CPD), and CO/CPD. Binary logistic regression models and generalized estimating equations models were analyzed by SPSS software, version 21 to determine the chances of quitting smoking. Results: Of the NP participants, 30.4% and 19.6% were abstinent after 2 and 6 months, respectively, while NL was found less effective with 19.7% for 2-month follow-up and 13.1% for 6-month follow-up. The 6-month success of quitting attempts was significantly different for the NP participants at the second half of Cot/CO (P=0.029). Of the NL participants, CO/CPD would be a superior predictor for smoking cessation success (P>0.05). Conclusion: The findings of this study suggested two markers of Cot/CO and CO/CPD in this order for the optimum treatment outcomes of NP and NL.

Objective(s): This study aimed at investigating the effect of serotonergic 5-HT4 receptor agonist/antagonist on memory consolidation deficit induced by ACPA (a potent, selective CB1 cannabinoid receptor agonist) in the pre-limbic (PL) cortex. Materials and Methods: We used the step-through passive avoidance test to evaluate memory consolidation of male Sprague-Dawley (SD) rats. Bilateral post-training microinjections of the drugs were done in a volume of 0.6 μl/rat into the PL area (0.3 μl per side).Results: The results showed a significant interaction between RS67333 hydrochloride (5-HT4 receptor agonist) or RS23597-190 hydrochloride (5-HT4 receptor antagonist) and ACPA on consolidation of aversive memory. RS67333 hydrochloride (0.5 μg/rat) enhanced consolidation of memory and its co-administration at the ineffective dose of 0.005 μg/rat with ineffective (0.001 μg/rat) or effective (0.1 μg/rat) doses of ACPA improved and prevented impairment of memory caused by ACPA, respectively. In other words, RS67333 had a bidirectional effect on ACPA-caused amnesia. While RS23597-190 hydrochloride had no effect on memory at the doses used (0.005, 0.01, 0.1, or 0.5 μg/rat); but its concomitant use with an effective dose of ACPA (0.1 μg/rat) potentiated amnesia. None of the drugs had an effect on locomotor activity.Conclusion: This study revealed that activation or deactivation of the 5-HT4 receptors in the PL may mediate the IA memory impairment induced by ACPA indicating a modulatory role for the 5-HT4 serotonergic receptors.

Sleep deprivation has deteriorating effects on cognitive functions and activation of brain inflammation mechanisms has been reported by some studies following total sleep deprivation. Some studies have reported the health benefits of punicalagin, a main abstract from Punica granatum L., including those for the treatment of Alzheimer’s disease. The antioxidant characteristic of punicalagin and the fact that sleep deprivation accelerates mediators of inflammation led us to further explore the possible neuroprotective role of punicalagin in total sleep deprivation memory impairment in a rat model. In this study, male Wistar rats were implanted with a canula in the lateral ventricle to receive intracerebroventricular injections (drug or vehicle). The animals were trained for the passive avoidance test and then received intracerebroventricular injections of different doses of punicalagin (0.001, 0.01, or 0.1 μg/rat). Then, they were placed in the sleep deprivation apparatus for 24 hours and tested afterwards for memory retrieval and locomotion. Our results indicated that 24 hours of total sleep deprivation impaired memory processes. PG microinjection before TSD did not prevent the deteriorating effect of total sleep deprivation on memory, and only showed a tendency of restoring the memory impairment. Comparison of the locomotor activity between the animals in different groups showed a significant increase in the total sleep deprivation sham groups that received two of the highest doses of punicalagin. Considering the reported beneficial actions of PG by other studies, further investigation is needed into the possible effects of PG in memory alterations.

Objective(s): Evidence shows that sleep deprivation (SD) disrupts the formation of hippocampus-related memories. Moreover, α2 adrenergic receptors that are wildly expressed in the CA1 hippocampal region have a significant role in modulating both sleep and memory formation. In the present research, we wanted to investigate the effect of stimulation and blockage of CA1 α2 adrenergic receptors by clonidine (an agonist of α2 adrenergic receptor) and yohimbine (an antagonist of α2 adrenergic receptor), respectively, on memory retention impairment induced by REM SD (RSD) in rats. Materials and Methods: Multiple platform apparatus were used to induce RSD, and the passive avoidance task was used to assess memory consolidation. Clonidine and yohimbine were injected intra-CA1. Results: The results showed that RSD (for 24 and 36, but not 12 hr) decreased memory retention, with no effect on locomotion. Post-training intra-CA1 infusion of a subthreshold dose of yohimbine (0.001 μg/rat) did not alter, while clonidine (0.1 μg/rat) restored memory retention impairment induced by RSD (24 and 36 hr). Also, none of the interventions did not influence locomotor activity. Conclusion: Our data strongly showed that CA1 α2 adrenergic receptors have a critical role in RSD-induced memory retention impairment.

Background: Critical analysis of new evidence in medical sciences relies on statistics in terms of correlation.The aim of the present study was to evaluate the correlation coefficients among the behavioral features in theoffspring of morphine-abstinent parent(s).Methods: The offspring of various types of parental morphine-exposure were divided into 4 groups includingoffspring of healthy parents (CTL), offspring of paternal morphine-abstinence (PMA), offspring of maternalmorphine-abstinence (MMA), and offspring of both morphine-abstinence (BMA). Pain perception,depression-like behavior, and avoidance memory in the offspring were quantified. The logical structure ofassociation was measured using the Pearson correlation analysis.Findings: A strong correlation was observed between pain and depressive-like behavior in female and maleoffspring of healthy parents. Moreover, in the male and female offspring of healthy parents and BMA, nosignificant correlation was observed between avoidance memory and pain behavior or depressive-likebehavior. However, in the offspring of MMA, a strong correlation was observed between avoidance memoryand depressive-like behavior.Conclusion: The results of the study signified the importance of correlation analysis in addictive behavior. Theresults revealed that the pattern of correlation of the behavior of the offspring of MMA and PMA differed

Introduction: Opioid addiction is an important concern in the World. Reports demonstrate that substance use disorder could influence genetic and environmental factors, and children of addicts have a higher rate of psychopathology. In this study, we investigated depression-like behavior among offspring of morphine-exposed rat parents. Methods: Adult male and female Wistar rats received morphine for 21 consecutive days and then let them were free of drugs for ten days. Offspring of these rats were divided into three distinct groups: maternal morphine-exposed, paternal morphine-exposed, and both maternal and paternal morphine-exposed. We used sucrose preference and Forced Swim Test (FST) to measure depression-like behavior. Also, we induced chronic mild stress using repeated corticosterone injection and evaluated depression-like behavior in offspring of morphine-exposed parents compared with offspring of healthy ones. Results: Results indicated that depression-like behaviors in the offspring of morphine-exposed rats were higher than those in the offspring of the control group in confronting with chronic mild stress. Additionally, mild chronic stress can produce an exaggerated effect on depression-like behavior in offspring of the morphine-exposed parent(s) compared with those of the control group. Conclusion: Our data support the previous hypothesis that the depression rate is higher in the children of addicts. We verified that even when mother or father was clean of opioid in the time of gestation, their children would be susceptible to depression. Dysregulation of hypothalamic-pituitary-adrenal axis and changing in neuronal features in the hippocampus increased depression-like behavior in the offspring of morphine-exposure parents.

Background: Sleep disorder or sleep deprivation (SD) is a common issue in today’s society. Numerous evidences show that sleep is essential for proper brain performance and cognitive processes; on the other hand, cognitive functions have a broad range with learning and long-term memory as the most important ones related to attention. Since many studies show that cholinergic system has a significant role in sleep, learning, and memory, this study aims to investigate the impacts of CA1 Cholinergic Nicotinic Receptors on memory acquisition deficit which is stimulated by total sleep deprivation (TSD) and REM sleep deprivation (RSD). Methods: In this study a water box or a multi-platform apparatus was used in order to induce TSD or RSD. In order to investigate interactions of cholinergic system and hippocampus-dependent memory, nicotinic receptor agonist (nicotine) or nicotinic receptor antagonist (mecamylamine) was injected in hippocampal CA1. Results: According to the results of this study, 24 hours TSD or RSD decreased memory acquisition and injection of nicotine (0.0001 µg/rat) or mecamylamine (0.001 µg/rat) in TSD and RSD sham groups didn’t change memory acquisition. However, injection of sub-threshold dose of nicotine (0.0001 µg/rat) and mecamylamine (0.001 µg/rat) could reduce negative effects of SD in both TSD and RSD. Conclusion: According to the present study, cholinergic nicotinic receptors are effective in learning and memory improvement.

Objective(s): Behavioral and neuroimaging studies have shown that transcranial direct current stimulation, as a non-invasive neuromodulatory technique, beyond regional effects can modify functionally interconnected remote cortical and subcortical areas. In this study, we hypothesized that the induced changes in cortical excitability following the application of cathodal or anodal tDCS over the left frontal cortex as pre-training would affect functional connectivity in resting-state circuits of fear memory and consequently could improve or disturb the acquisition of fear memory. Materials and Methods: In order to evaluate the polarity-dependent effects of tDCS on the acquisition of fear memory and the functional connectivity, we applied left prefrontal anodal or cathodal stimulation at 200 μA for one session to healthy mice for the durations of 20 and 30 min prior to fear conditioning. Results: Our results revealed that the administration of left prefrontal anodal (for both 20 and 30 min durations) and cathodal (at 30 min duration) tDCS impaired the acquisition of both contextual and cued fear memory. In addition, we did not observe a direct correlation between stimulation duration and the efficacy of tDCS on the acquisition of contextual and cued fear memory. Conclusion: In this study, the impairments of both contextual and cued memory further confirmed the previous studies reporting that the administration of transcranial stimulation would affect the activity of deeper structures like amygdala and hippocampus as the main components of the fear memory circuit in acquisition, storage, and expression of the memory.

Introduction: 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. Methods: 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). Results: 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). Discussion: 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.

The purpose of this study was to investigate the effect of electrical stimulation on sciatic nerve regeneration and functional recovery of target muscles. Mice were randomly divided into 3 groups: ligated without electrical stimulation, ligated with electrical stimulation and control (non-ligated). The unilateral peripheral mononeuropathy was produced on the right hind limb. Sciatic nerve was then electrically stimulated daily for a period of 2 weeks (duration: 0.2 msec, frequency: 100Hz, amplitude: 15mA). Evoked surface EMG was recorded from biceps femoris (BF) and gluteus maximus (GM) muscles on the 3rd, 7th, 10th and 14th day after sciatic nerve ligation. Muscle force and sensitivity was determined by processing of the recorded EMG signals in time and frequency domains respectively. The results showed electrical stimulation (ES) produced a significant increase in the EMG response of BF, and muscle force significantly increased on the 14th day (p

ABSTRACT Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been identified as the well-known coordinator of intracellular antioxidant defense system. Herein, we aimed to evaluate the effects of Nrf2 silencing on mitochondrial biogenesis markers peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), nuclear respiratory factor-1(NRF-1), mitochondrial transcription factor A (TFAM) and cytochrome c as well activities of two enzymes citrate synthase (CS) and malate dehydrogenase (MDH) in three brain regions hippocampus, amygdala, and prefrontal cortex of male Wistar rats. Small interfering RNA (siRNA) targeting Nrf2 was injected in dorsal third ventricle. Next, western blot analysis and biochemical assays were used to evaluation of protein level of mitochondrial biogenesis factors and CS and MDH enzymes activity, respectively. Based on findings, whilst Nrf2-silencing led to notably reduction in protein level of mitochondrial biogenesis upstream PGC-1α in three brain regions compared to the control rats, the level of NRF-1, TFAM and cytochrome c remained unchanged. Furthermore, although Nrf2 silencing increased CS activity, activity of MDH significantly decreased in hippocampus and prefrontal cortex areas. Interestingly, CS and MDH activities in amygdala did not change after Nrf2 knockdown. In conclusion, the present findings highlighted complexity of interaction of Nrf2 and mitochondrial functions in a brain region-specific manner. However, by outlining the exact interaction between Nrf2 and mitochondria, it would be possible to find a new therapeutic strategies for neurological disorders related to oxidative stress.

Introduction: Association between single-nucleotide polymorphisms (SNPs) in mu opioid receptor gene and drug addiction has been shown in various studies. Here, we have evaluated the existence of polymorphisms in exon 3 of this gene in Iranian population and investigated the possible association between these mutations and opioid addiction. Methods: 79 opioid-dependent subjects (55 males, 24 females) and 134 non-addict or control individuals (74 males, 60 females) participated in the study. Genomic DNA was extracted from volunteers’ peripheral blood and exon 3 of the mu opioid receptor gene was amplified by polymerase chain reaction (PCR) whose products were then sequenced. Results: Three different heterozygote polymorphisms were observed in 3 male individuals: 759T>C and 877G>A mutations were found in 2 control volunteers and 1043G>C substitution was observed in an opioid-addicted subject. Association between genotype and opioid addiction for each mutation was not statistically significant. Discussion: It seems that the sample size used in our study is not enough to confirm or reject any association between 759T>C, 877G>A and 1043G>C substitutions in exon 3 of the mu opioid receptor gene and opioid addiction susceptibility in Iranian population.

Introduction: The mechanisms of hepatic encephalopathy are not fully understood. Moreover, there is no comprehensive data concerning the effects of nitric oxide (NO) system on anxiolytic-like behaviors induced by bile duct ligation (BDL). Methods: Male mice weighing 25-30 g were used and anxiety-like behaviors were tested using hole-board task. Results: The data indicated that cholestasis increased the number of head-dipping but did not alter other aspects of behavior, 7 days after BDL, suggesting an anxiolytic-like response. Furthermore, the results showed that intraperitoneal (i.p.) injection of L-arginine (200 and 250 mg/kg) 15 min before testing induced anxiolytic-like behaviors in the normal animals, 4 and 7 days after BDL (considering that the dose of 200 mg in the normal mice is ineffective but is effective in the BDL mice). On the other hand, injection of L-NAME (35 and 45 mg/kg, i.p.) 15 min before testing induced anxiogenic-like behaviors in the normal animals, 4 and 7 days after BDL (the dose of 35 mg/kg in the normal mice is ineffective but is effective in the BDL mice ). Moreover, injection of ineffective doses of L-NAME (25 and 35 mg/kg, i.p.) 15 min before administration of L-arginine (250 mg/kg, i.p.) and 7 days after BDL, decreased anxiolytic-like behaviors, signi.cantly. Discussion: Cholestatic mice show anxiolytic-like behaviors suggesting the involvement of the nitric oxide system.

Effects of intra-central amygdala administration of L-arginine, a nitric oxide precursor, and NG-nitro-L-arginine methyl-ester (L NAME), a nitric oxide synthase inhibitor, on the morphine-induced sensitization and also on the expression of morphine-induced place conditioning in rats were studied. Subcutaneous (s.c.) administration of morphine (2.5, 5 and 7.5 mg/kg) induced place conditioning. Repeated pretreatment of morphine (5 mg/kg, i.p.) followed by 5 days no drug treatment, increased place conditioning induced by morphine (0.5 mg/kg). Repeated intra-central amygdala administration of L-arginine (0.3, 1 and 3 μg/ rat), with morphine during acquisition of sensitization, significantly increased or reduced morphine place conditioning in sensitized rats. The drug administration before testing also increased and reduced the expression of morphine place conditioning in sensitized animals. Repeated intra-central amygdala injections of L-NAME (0.3, 1 and 3 μg/rat) with morphine during acquisition of sensitization, reduced the acquisition of morphine place conditioning in the sensitized animals. The drug injection before testing also reduced morphine-induced conditioning. The results indicate that nitric oxide (NO) within the central amygdala may be involved in the acquisition and expression of morphine place conditioning in morphine-sensitized rats.

Effects of intra-central amygdala administration of L-arginine, a nitric oxide precursor, and NG-nitro-L-arginine methyl-ester (L NAME), a nitric oxide synthase inhibitor, on the morphine-induced sensitization and also on the expression of morphine-induced place conditioning in rats were studied. Subcutaneous (s.c.) administration of morphine (2.5, 5 and 7.5 mg/kg) induced place conditioning. Repeated pretreatment of morphine (5 mg/kg, i.p.) followed by 5 days no drug treatment, increased place conditioning induced by morphine (0.5 mg/kg). Repeated intra-central amygdala administration of L-arginine (0.3, 1 and 3 μg/ rat), with morphine during acquisition of sensitization, significantly increased or reduced morphine place conditioning in sensitized rats. The drug administration before testing also increased and reduced the expression of morphine place conditioning in sensitized animals. Repeated intra-central amygdala injections of L-NAME (0.3, 1 and 3 μg/rat) with morphine during acquisition of sensitization, reduced the acquisition of morphine place conditioning in the sensitized animals. The drug injection before testing also reduced morphine-induced conditioning. The results indicate that nitric oxide (NO) within the central amygdala may be involved in the acquisition and expression of morphine place conditioning in morphine-sensitized rats.

ABSTRACTIntroduction/Aims: The nucleus accumbens (NAc) receives histaminergic neurons from tuberomammillary nuclei. There are also reports indicating that central histamine systems are involved in many physiological behavioral processes, including anxiety. The aim of the present study was to assess whether the histaminergic system of the NAc is involved in the anxiety-related behaviors. Methods: As a model of anxiety the elevated plus maze which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents was used in male Wistar rats. Results:Intra-NAc administration of histamine (0.01, 0.1 and 1 μg/rat) increased the percentage of open arm time (%OAT) and open arm entries (%OAE) but not locomotor activity, indicating an anxiolytic response. Furthermore, bilateral microinjections of different doses of the H1 receptor antagonist pyrilamine (0.001, 0.01, 0.1 and 1 μg/rat) or the H2 receptor antagonist ranitidine (0.001, 0.01, 0.1 and 1 μg/rat) into the NAc increased %OAT and %OAE but not locomotor activity. However, both histamine and histamine receptor antagonists showed an anxiolytic-like effect, the antagonists (1 μg/rat) also decreased the histamine response. Discussion: The results may indicate a modulatory effect for the H1 and H2 histamine receptors of nucleus accumbens in the anxiety behavior of rats.

"n Objective: "n The nucleus accumbens (NAc) receive histaminergic neurons from tuberomammillary nuclei. There are reports indicating that central histamine systems are involved in many physiological behavioral processes, including anxiety. The aim of the present study was to assess whether the histaminergic system of the NAc is involved in anxiety-related behaviors. Methods: Rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then were placed in a stereotaxic apparatus. In addition, two stainless-steel cannuale were placed 2 mm above the nucleus accumbens shell. Seven days after recovery from surgery, the behavioral testing was started. As a model of anxiety, the elevated plus maze which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used in male Wistar rats. "nResults: Intra-NAc administration of histamine (0.01, 0.1 and 1 µg/rat) increased the percentage of open arm time (%OAT) and open arm entries (%OAE) ,but not locomotor activity, indicating an anxiolytic response. Furthermore, bilateral microinjections of different doses of the H1 receptor antagonist pyrilamine (0.001, 0.01, 0.1 and 1 µg/rat) or the H2 receptor antagonist ranitidine (0.001, 0.01, 0.1 and 1 µg/rat) into the NAc increased %OAT and %OAE , but not locomotor activity. However, both histamine and histamine receptor antagonists showed an anxiolytic-like effect ; the antagonists (1 µg/rat) also decreased the histamine response. "n "n Conclusion: The results may indicate a modulatory effect for the H1 and H2 histamine receptors of nucleus accumbens in the anxiety behavior of rats.

In the present study, interactions between lead exposure with nitric oxide precursor (L-arginine) or nitric oxide synthase (NOS) inhibitor (L-NAME) on naloxone-induced jumping and diarrhea in morphine-dependent mice were examined. Chronic lead acetate (0.05%) exposure altered naloxone-induced jumping and diarrhea in mice. Jumping was decreased after 7 days and was unchanged 14 and 28 days after lead exposure. Diarrhea was only increased 28 days after lead exposure, which shows a difference between two signs of withdrawal syndrome. Since jumping is the most important sign, the animals were exposed to lead for 7 days in the rest of experiments. In a set of experiments, the nitric oxide agents (L-arginine) or L-NG-nitro arginine methyl ester (L-NAME) were used before naloxone injection to test their effects on the expression of jumping. The low dose of L-arginine, a precursor of nitric oxide (20 mg/kg) decreased jumping, but increased diarrhea. Higher dose of L-arginine (80 mg/kg) increased jumping, while decreased diarrhea. L-NAME decreased both jumping and diarrhea. On the other hand, L-arginine in combination with lead reversed lead-induced attenuation of naloxone-induced jumping, while decreased diarrhea. L-NANE in combination with lead decreased diarrhea, while did not alter jumping. In the second set of experiments, nitric oxide drugs were injected during development of morphine dependency. Data showed that jumping was increased or decreased by low or higher dose of L-arginine respectively. Diarrhea was also increased by the drug. L-NAME decreased both jumping and diarrhea in the development of morphine dependency. Both L-arginine and L-NAME in combination with lead decreased lead-induced jumping and diarrhea. It is concluded that nitric oxide may modulate morphine withdrawal signs and lead-induced attenuation of jumping.

"nObjective:The influence of cholinergic drugs on lithium-induced statedependent learning has been investigated in adult male mice. "nMethod: A single-trial step-down inhibitory avoidance task was selected. The drugs used in the study were lithium chloride physostigmine , nicotine hydrogen tartrate and scopolamine hydrobromide, atropine sulphate. The drugs were administrated through the peritoneal route. Control animals received saline or respective vehicle for nicotine. Ten animals were used in each experimental group. on day 1 or training session, the animals being trained in the step-down inhibitory avoidance task, and then immediately received post-training treatment of lithium or atropine or scopolamine. On day 2 or testing session, the animals firstly received pre-test administration of drugs (for nicotine 30 min, for lithium 45 min and for cholinergic antagonists 60 min before the test), and then were tested for step-down latency. "nResults:The results showed that post-training and pre-test intraperitoneal (i.p.) administration of lithium (10 mg/kg) induced state-dependent learning. In addition, pre-test administration of an anticholinesterase, physostigmine (0.3 and 0.6 mg/kg, i.p.) and nicotinic acetylcholine receptor agonist, nicotine (0.1 and 0.5 mg/kg) could substitute for pre-test lithium. Pre-test coadministration of an ineffective dose of physostigmine (0.1 mg/kg) but not nicotine (0.01 mg/kg), with lower doses of lithium (2.5 and 5 mg/kg) potentiated the effect of the latter drug on step-down latency. Post-training administration of a nonselective antagonist of muscarinic acetylcholine receptors, atropine, decreased the step-down latency, but pre-test administration of the same dose of the drug and also lithium, could not reverse the decrease of step-down latency. On the other hand, pre-test atropine at higher doses (0.3 and 0.6 mg/kg) disrupted lithium-induced statedependent learning. On the contrary, the decrease of step-down latency due to post-training administration of another nonselective muscarinic antagonist, scopolamine (1 mg/kg, i.p.) reversed by pre-test administration of not only the same dose of the drug, but also lithium (10 mg/kg). Interestingly, pre-test administration of scopolamine (1 mg/kg) also reversed the decrease of stepdown latency induced by post-training lithium (10 mg/kg). "nConclusion: cholinergic system(s) may be involved in the lithium-induced state- dependent learning and the involvement of muscarinic receptors is more possible than nicotinic ones.

Neural Cell Adhesion Molecules (NCAMs) are known to influence memory by affecting neural cell-cell and cell-extracellular matrix junctions. This study investigated the possible role of cAMP pathway in the expression of hippocampal NCAM and its polysialylated derivative (PSA-NCAM). The following pharmacological tools were employed for manipulation of cAMP pathway: a) forskolin; the activator of adenylyl cyclase (AC), b) 8-Br-cAMP; a protein kinase A (PKA) agonist, c) 8-pCPT-2'-O-Me-cAMP; a selective enhancer of exchange protein activated by cAMP (Epac) and d) Rp-cAMP; a PKA inhibitor. Memory acquisition was tested by passive avoidance paradigm after injecting the above compounds for three consecutive days into the CA1 region of dorsal hippocampus of rats. Forskolin and 8-Br-cAMP enhanced memory retrieval while Rp-cAMP significantly reduced memory and NCAM levels. 8-pCPT-2'-O-Me-cAMP failed to alter memory performance or NCAM levels as compared to vehicle. We observed no significant changes in PSA-NCAM, however the expression of St8sia4 and St8sia2 (the polysialyltransferase isoforms) were altered. The mRNA levels of St8sia4 was down-regulated by 8-Br-cAMP, Rp-cAMP and 8-pCPT while forskolin led to almost 3 and 5 fold increase in mRNAs of St8sia2 and St8sia4, respectively. The current insight might endorse the predominant role of PKA as compared to Epac in cAMP pathway in expression of NCAM and memory function.

The fifth Iranian national congress on the biology of addiction was held in 22-24 June 2011 in Tehran University of Medical Sciences with over 100 valuable oral and poster presentations and over 300 participants. One of the main sessions of the congress was devoted to a national strategic planning and Iranian Drug Control Head Quarter (DCHQ) introducing the first national executive road map on research into the biology of addiction. The road map will serve as a part of national strategic plan on addiction studies in Iran. As the main contributors in the preparation of the map, we think neuroscientists have to play a unique role in implementation of this map. We believe that the studies into the biology of addiction can act as a pivotal turning point to promote neuroscience in Iran regarding the governmental focus and public demand on addiction prevention and treatment. In this editorial, we will elucidate a general schema of the map, focusing more on potential opportunities for neuroscientists, and discuss new hopes, needs and challenges that we would be facing in the future to take advantage of addiction related opportunities to study neuroscience in both national and international levels.

Abstract The nucleus accumbens shell (NAcSh) plays a role in appetitive and negative motivation with sex differences in responses. NAcSh and its laterality in metabolic and hormonal responses to chronic stress in female rats is evaluated via transient inactivation of this nucleus during stress induction. Animals in the stress groups received consecutive stress for four days and transient inactivation of NAcSh was performed by administrating lidocaine (0.2%) unilaterally or bilaterally in the nucleus for five minutes before electric foot shock induction. After stress termination, food and water intake, latency to eat, plasma glucose, corticosterone, estradiol and progesterone were measured in all groups. Results showed that stress increased food intake and blood glucose level, but there were no change in the latency to eat and the amount of water intake. The right side, the left side, and both sides of NAcSh may be dominant in latency to eat, food intake, and both water intake and plasma glucose level, respectively. Although chronic stress included no changes for corticosterone and progesterone, it increased estradiol level in plasma. Also, bilateral and right sides of NAcSh may have modulatory effects on stress in corticosterone and progesterone, respectively, without affecting estradiol. It can be concluded that the NAc shell plays a pivotal role in metabolic and hormonal responses to chronic stress in a laterality manner in female rats.