فهرست مطالب mohammad-reza zarrindast

N-methyl-D-aspartate (NMDA) receptors hold profound importance in shaping an individual’s mental and physical health. These receptors, forming heterotetrametric complexes, play a pivotal role in synaptic plasticity, learning, and memory. Dysfunction in NMDA receptors has been associated with a spectrum of neurological and psychiatric disorders, including Alzheimer’s disease, schizophrenia, depression, and Attention-Deficit Hyperactivity Disorder (ADHD). The intricate regulatory mechanisms of these receptors, involving subunit diversity, allow for fine-tuning of synaptic transmission. Therapeutically, drugs targeting NMDA receptors, such as ketamine for depression, underscore their crucial role in mental health. Ongoing research explores their involvement in physical health, with potential implications for conditions like ADHD. Understanding and modulating NMDA receptor function emerge as critical endeavors for promoting comprehensive well-being, highlighting the intricate interplay between molecular processes and overall health outcomes.In this context, the present research aims to unravel the specific interplay between NMDA receptor subunits NR1 and NR2 and ADHD. It aims to elucidate the potential role of NR1 and NR2 receptors in the pathophysiology of ADHD and contribute valuable insights that may pave the way for more targeted therapeutic interventions in ADHD and potentially other neuropsychiatric disorders.

The study involved 70 male participants aged 6 to 15 years, comprising 50 individuals diagnosed with mixed ADHD and 20 age-matched healthy controls. Participants meeting DSM-IV criteria for mixed ADHD were recruited from the rehabilitation clinics in Tehran, Iran. Inclusion criteria specified ages between 6 and 15 years. Exclusively male participants were selected to minimize potential gender-related confounding factors. Additionally, individuals with a history of neurological or neuropsychological problems and severe physical illness were excluded from the research. Healthy controls were recruited through advertisements targeting children in some schools, screened, and matched for age and gender.ADHD participants underwent a comprehensive diagnostic assessment conducted by an expert clinician involving pre-assessment questionnaires, semi-structured interviews aligned with DSM-5 criteria, and administration of the K-SADS-PL and IVA2 tests for enhanced diagnostic validity. The K-SADS-PL screening interview focused on ADHD symptoms, with responses rated on a scale. The IVA2 assessed attention and impulsivity through responses to auditory and visual stimuli and total attention quotient. Blood samples drawn without specific timing or fasting requirements were collected from both study and control groups, processed, and stored at -80°C. Serum samples were later used to quantify NR1 and NR2 receptor expression through western blotting, with fluorescence visualization and computer-assisted analysis software for relative abundance determination. All analyses were performed using SPSS software version 26.

The investigation revealed noteworthy distinctions in the mean expression levels of NR1 and NR2 receptors between the experimental group (ADHD) and the healthy control group. Specifically, the mean expression of NR1 receptors in the ADHD group was found to be 97.7, significantly lower than the corresponding mean expression of 124.25 observed in the healthy control group, as indicated by the p-value of P<0.00001, denoting statistical significance at P<0.05. Similarly, the mean expression of NR2 receptors in the ADHD group, quantified at 154.6, demonstrated a significant variance from the mean expression of 173.25 in the healthy control group, corroborated by a p-value of P<.00001, thereby establishing statistical significance at P<0.05. These findings underscore the substantial disparities in the expression profiles of NMDA glutamate receptors in individuals with ADHD compared to their neurotypical counterparts, providing valuable insights into the molecular underpinnings of this neurodevelopmental disorder. The decrease in the expression of these proteins in the ADHD group causes a decrease in cognitive symptoms, including attention quotient, in this group compared to healthy people.

The current study revealed a significant link between ADHD and abnormal expression of NMDA glutamate receptors, particularly the NR1 and NR2 subunits, in the blood plasma of individuals with ADHD compared to healthy controls. This suggests a potential role for NMDA receptors in ADHD’s pathophysiology, implying that impaired NMDA receptor function may contribute to the disorder’s development. Dysfunctional NMDA receptors can impact dopamine and epinephrine levels in the brain, influencing ADHD symptoms. Notably, disruptions in NMDA receptors can lead to excessive and insufficient dopamine levels, contributing to hyperactivity, impulsivity, attention regulation difficulties, motivation, and focus issues. The findings highlight the need for a more comprehensive understanding of ADHD’s neurobiological foundations and suggest potential therapeutic avenues targeting NMDA receptor function. Additionally, the study contributes to personalized medicine in ADHD and has broader implications for understanding brain function in neuropsychiatric disorders influenced by glutamatergic signalling, offering insights that deepen our comprehension of ADHD, provide therapeutic potential, and contribute to a broader understanding of brain function in neuropsychiatric contexts.

The opiate dosage adequacy scale (ODAS) is one of the most common assessment tools in studies on substance use disorders, which evaluates the “adequacy” of opiate medication doses in individuals recruited in maintenance approaches. There is no investigation on the Persian version of this questionnaire in Iran. This research validated a Persian version of the ODAS. 

The Persian version of the ODAS was translated and revised based on the original scale presented by González-Saiz et al. The psychometric characteristics of the ODAS were assessed via direct interviews. Three trained interviewers questioned 250 patients treated in methadone maintenance clinics in Mazandaran Province (Northern Iran) for more than three months. Internal consistency and factor analysis were conducted using SPSS software, version 24.

The internal consistency of ODAS was satisfactory (Cronbach’s α=0.81). Across all items, considerable inter-rater reliability was discovered (kappa values between 0.90 and 1). A four-component structure was produced by the factor analysis that accounted for 77.5% of the total variance. Cronbach’s α coefficients of the four components of Heroin craving and overmedication, Consumption, objective opiate withdrawal symptoms, and subjective opiate withdrawal symptoms were 0.84, 0.91, 0.83, and 0.74, respectively.

The reliability and validity of the Persian version of the ODAS were satisfactory in a sample of methadone maintenance subjects.

Negative early-life experiences (e.g. having an aggressive father) can leave long-lastingimpacts on the behavior. However, it is not clear if they influence learning and memory. 

In this study, we investigated the influences that the presence of an aggressive father had on the level of passive avoidance learning and spatial memory. We also studied the changes in the dopamine receptor D2 (DRD2) and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) gene expression in the hippocampus. Then, we evaluated if a DRD2 antagonist (sulpiride, 0.125, 0.25, or 0.5 μg/rat) could modulate these changes. 

We found that the subjects exposed to early-life stress made by aggressive fathers had impaired passive avoidance learning and spatial memory compared to subjects with normal fathers. Treatment with sulpiride improved passive avoidance learning and spatial memory in rats with aggressive fathers. The rats with aggressive fathers also had higher expression of the DRD2 gene in their hippocampus than those with normal fathers, while the PGC-1α gene expression was not different among groups. Treatment with sulpiride (0.125, 0.25, or 0.5 μg/rat) reduced the DRD2 gene expression in those with aggressive fathers to the normal level compared to those with normal fathers. 

These data suggest that having and living in a shared place with an aggressive father, even without any physical contact, can detrimentally affect passive avoidance learning and spatial memory which is accompanied by the increased expression of the DRD2 gene. Also, sulpiride as a dopaminergic antagonist could reverse this process.

Anxiety is one of the comorbid disorders of opioid addiction, which leads to opioid abuse or persuades people to engage in opioid abuse. Evidence revealed that morphine exposure before conception changes the offspring’s phenotype. The current study aimed to investigate the influence of morphine dependence and abstinence on anxiety-like behavior in morphineexposed and drug-naïve offspring. Adult male and female rats were treated with morphine or vehicle for 21 days. Then, all rats were left without drug treatment for 10 days. A morphine-exposed female rat was mated with either a vehicle-exposed or morphine-abstinent male. According to parental morphine exposure, the offspring were categorized into four distinct groups: (1) control (both drug-naïve parents), (2) paternal morphine-exposed, (3) maternal morphine-exposed, and (4) biparental morphine-exposed. The anxiety-like behavior was measured in adult male offspring using open field and elevated plus-maze tests before morphine exposure (naïve), 21 days after morphine exposure (dependence), and ten days after the last morphine exposure (abstinence).  The results indicated that anxiety-like behavior increased before morphine exposure in maternal and biparental morphineexposed offspring (P<0.05). However, after morphine exposure, the anxiety level did not change among the groups. Ten days after the last morphine exposure, anxiety-like behavior increased only in biparental morphine-exposed offspring (P<0.05).  The offspring of morphine-abstinent parents exhibited an anxious phenotype. Disruption of the HPA axis was seen in the progeny of maternal and biparental morphine-exposed rats. Indeed, morphine exposure for 21 days did not change anxiety-like behavior in these offspring which might be correlated to disruption of HPA axis in them.

Opiates dependence has many side effects on body especially brain neuroplasticity leading to changes in behavior. In this study, we evaluated the effects of morphine dependence on learning and memory as well as on Peroxisome proliferator-activated receptor gamma coactivator -1 alpha (PGC-1α) protein level as a key regulator of mitochondrial biogenesis. Also, by using Chloroquine (lysosomal inhibitor) and dopaminergic system inhibitor (Sulpiride), the molecular mechanism, underling morphine addiction related to lysosome, dopamine receptors and mitochondria, has been considered in this study.

Male albino Wiastar rats received morphine in their water for 21 days; during the ending 4 days, they received daily intracerebroventricular (i.c.v.) injection of Chloroquine diphosphate (50 mM). Also, i.c.v. injection of Sulpiride (0.25μg/rat) was done before behavioral test. Shuttle box apparatus was used for learning and memory evaluation. After behavioral test, the brains of rats were extracted and the level of PGC-1α protein was investigated by western blotting.

Results indicated that morphine oral administration has reduced learning and memory-like behavior. Pre-training i.c.v. injection of Chloroquine and Sulpiride improved learning and memory. PGC-1α protein level in rats which received Chloroquine and also in the morphine group increased and there was a more significant increase in rats which received morphine, Chloroquine and Sulpiride altogether.

Morphine has an adverse effect on learning and memory as it has been shown with spending more time in dark rooms of Shuttle box apparatus, which was reversed by Chloroquine (lysosomal inhibitor) and dopamine inhibitor (Sulpiride). Increasing PGC-1α protein level may imply the important role of mitochondrial biogenesis in morphine-dependent learning changes. Overall, data suggest dopaminergic system along with lysosome and mitochondrial activity play an important role in morphine addiction status.

Autism spectrum disorder (ASD) is identified by developmental deficits that lead to repetitive/stereotypic patterns of behavior and impaired social interactions. Studies have been indicated that exercise can decrease stereotypic behaviors in animal models of ASD. This research was designed to discover the effects of different models of forced exercise on stereotypical behaviors in a rat model of ASD induced by thi-merosal (THIM).

Fifty-six male Wistar rats were divided into eight groups. The rats were received saline (1 ml/kg) or THIM (300 μg Hg/kg) by four intramuscular injections on 7, 9, 11, and 15 postnatal days. The rats were also treated by several protocols of treadmill exercise, including non-sedentary, sedentary, protocol 1, protocol 2, and a combination of protocols 1 and 2.

Our study showed that THIM decreased the grooming time compared to the control group. Moreover, protocol 2 exercise significantly decreased grooming time in stranger zone 2 compared to the THIM group.

Our results showed that stereotypical behaviors exagger-ated by THIM and moderate exercise could improve ASD-associated behaviors in the THIM-treated rats. Hence, moderate exercise may be a useful protocol for the treatment of ASD.

Multiple Sclerosis (MS) is a chronic, autoimmune and progressive neurological disease that causes a wide range of cognitive deficits in patients by destroying the Central Nervous System (CNS). This study aims to examine the effect of Transcranial Direct Current Stimulation (tDCS) on working memory of patients with MS.

For this purpose, a quasi-experimental pre-t-est, post-test design with the control group was considered. In total, 32 patients with relapsing-remitting MS were selected using the convenience sampling method and randomly divided into experimental and control groups. The intervention consisted of 10 sessions of cranial electrical stimulation, during which the participants were divided into two groups receiving real and sham stimulation. N-Back test was employed to evaluate working memory.

The data were analyzed using the independent t-test. The results revealed that working memory was improved in the experimental group compared to the control group (P<0.05).

It could be concluded that anodal tDCS over the right dorsolateral prefrontal cortex (R-DLPFC) appears to be a promising therapeutic tool for cognitive dysfunction among patients with MS.

Multiple sclerosis is a de-myelinating inflammatory condition of the central nervous system that is often thought of as an autoimmune disorder. These patients suffer from extensive cognitive impairments such as poor attention and concentration and memory and processing speed; Therefore, the aim of this study was to investigate the anodic effect of direct cortical electrical stimulation (tDCS) on sustained attention performance in patients with multiple sclerosis (MS) in a pretest-posttest design with a control group. For this purpose, 32 patients with MS were selected using available sampling method and randomly assigned to experimental and control groups. The intervention consisted of 10 sessions of direct electrical stimulation during which patients were divided into two groups, one group received real stimulation and the other group received sham stimulation or sham. The research instruments were the use of RTI and RVP subtests in CANTAB test. Data analysis was performed based on independent and dependent t-test to compare pre-test and post-test scores in experimental and control groups. The results showed an improvement in sustained attention and processing speed in the experimental group at a significant level of 0.05. Therefore, we conclude that transcranial electrical stimulation of the brain improves sustained attention deficit and speed of response in patients with MS.

Tumor Necrose Factor-alpha (TNF-α) changes by REM sleep deprivation. Some believe that TNF-α is a biomarker in the deprivation of REM sleep. The patients with insomnia could be better after using Anti TNF-α or Infliximab (IFX), on the other hand, IFX effects on Patient Tolerance Threshold (PTT). Trying to manage the hospital inpatients’ pain is one of the common aims specially for intensive care unit patients.

 An experimental study with 72 male Wistar rats in 9 groups that each of groups include 8 rats and approved according to the ethics code in ethics committee of Tehran medical sciences university (CNS.Protocol-ICSS-940816). IFX was administered and it showed the time of the latency changed as PTT.

A significant difference between saline and IFX 0.2 mg/kg (F2 = 8.363, (P = <0.001)) in the time of latency observed.

REM sleep deprivation effects on TNF-α and IFX change the PTT in a Wistar rat model. So, these findings could be considered complex for patients and must to manage.

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]).

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.

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). 

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.

Depression is a common mood disorder in patients with Parkinson’s disease (PD), which negatively influences the quality of life and enhances caregiver burden. MLC901, a traditional medicine, has been demonstrated to be useful in preclinical and clinical studies. The aim was to study the effect of MLC901 on depression behavior in a mouse model of PD, comprising in the unilateral striatal delivery of the neurotoxin 6-hydroxydopamine (6-OHDA).

Female NMRI mice were divided into the following groups: sham/saline group, 6-OHDA/saline group, sham/MLC901 (40μg/kg) group and 6-OHDA/MLC901 group. Intraperitoneal treatments of MLC901 were started one week after the stereotaxic surgery that continued for 4 weeks (5 days/week). Locomotion was monitored using an openfield test and depressive-like responses were measured by forced swim test (FST) and tail suspension test (TST).

We found that MLC901 prevented the increased immobility time in the PD mice in both FST and TST, suggesting an antidepressant efficacy for the MLC901. None of the treatments alter locomotion compared to the sham group.

In conclusion, we propose that MLC901 is a potential candidate to be used in studies for the treatment of depression in PD.

Tramadol induces its unique effects through opioid pathways, but the exact mechanism is not known. The study aims to evaluate changes in the level of mu-opioid receptor (μOR), delta-opioid receptor (δOR), and phosphorylated cyclic adenosine monophosphate (cAMP) response element-binding protein (p-CREB) in the hippocampus (HPC) and amygdala (AL) areas of tramadol-treated rats.

For this purpose, a total of 36 male rats were divided into two main groups for chronic or acute tramadol exposure. The animals were then exposed to 5 mg.kg-1 of tramadol, 10 mg.kg-1 of tramadol, and normal saline. The HPC and AL areas of the animals were dissected upon completion of the period. The levels of p-CREB and μOR were quantified using the western blotting technique. The data were subjected to analysis of variance (ANOVA) followed by Tukey’s post-hoc analysis. The differences with the P-value lower than 0.05 were considered as significant.

In the HPC and AL areas of the brain, the level of μOR was decreased by acute tramadol exposure, while no significant difference was observed by chronic tramadol exposure. Moreover, results showed that the level of p-CREB dose-dependently increased by acute and chronic tramadol exposure.

HPC and AL are essential in the control of tramadol abuse. Tramadol abuse affects gene expression and transcription factors such as CREB. With acute drug tramadol treatments, the level of cAMP response element-binding protein (CREB) rapidly increases, while by chronic tramadol treatment, “peak and trough pattern is observing”. The activation of the rewarding mechanism is a precise instance of addictive behavior in tramadol-treated individuals.

Injection of l-arginine, a precursor of nitric oxide, in the rat’s hippocampus or periaqueductal gray matter reduces the analgesic effect of morphine on formalin-induced pain, but the effect of simultaneous injection of the substance in both areas have not been shown as our purpose of this research.

Wistar rats were used as control, morphine, and l-arginine groups. The rats were simultaneously cannulated in two areas of the dorsal hippocampus and laterodorsal PAG. One week later, the control animals received 50 μl of 2.5% formalin in the paw of the left foot under restrainer. The morphine group 10 min before formalin received the opioid (6 mg/kg, intraperitoneally). Other groups took l-arginine (0.25-2 µg/rat) in only one area (d hippocampus or ld PAG), prior to morphine administration. The effective dose of l-arginine (0.5 µg/rat) simultaneously was injected in both areas. The findings were analyzed by analysis of variance (ANOVA) under α=0.05.

Morphine induced analgesic response. Injection of NO precursor both separately and simultaneously in the two nuclei reduced morphine-induced analgesia.

Increasing levels of NO due to exclusive or concurrent injection of l-arginine in the areas likely antagonize the morphine response.

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.

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).

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.

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.

Acute and chronic failure in liver function may give rise to cognitive and non-cognitive impairments in the brain, namely hepatic encephalopathy (HE). Liver diseases may cause cholestasis, which is defined as the impaired secretion of bile. It is characterized by the accumulation of substances in plasma that are normally excreted in bile such as bile acids. Cholestasis can lead to hepatic encephalopathy. Several investigations have indicated that HE induces several symptoms, such as the impairment of learning and memory, anxiolytic-like behaviors, alterations in sleep pattern, and tremors. It has been reported that after HE, all classical neurotransmitter systems such as opioidergic, dopaminergic, cholinergic, GABAergic, adrenergic, serotonergic, and glutamatergic systems can be altered. This review focuses on cholestasis, hepatic encephalopathy, and behavioral disorders.

Context:

Nowadays, experiencing occasional anxiety is a common part of each person’s life. The number of anxious people has increased in this modern life style. This study aimed to review some researches as to accelerate searching for new anxiolytic treatments.

Evidence Acquisition:

Related articleswere extractedfrom databases includingPubMed, Google Scholar, Springer, ScienceDirect and Wiley.Forty-eight articles were chosen. The articles were carefully considered, and after extracting information, they were categorized and integrated in the appropriate sequences to meet the needs of this study.

This review mentions the important brain regions involved in anxiety; it then continues with encapsulating some of the neurotransmitters’ and neuropeptides’ functions that cope with anxiety-like behaviors.

With regard to the results, it is suggested that anxiety can be caused by change in the brains’ neurotransmitters level but more studies are needed to identify its exact mechanism.

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.

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.

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.

Our data strongly showed that CA1 α2 adrenergic receptors have a critical role in RSD-induced memory retention impairment.

Sleep deprivation (SD) in the long term can cause multi-organ dysfunction as well as neurocognitive disorders. Daytime sleep or napping is a biological compensate due to insomnia or sleep deprivation. Metabolic responses to this biological rhythm may being as a biological indicator or biomarker to compare the effect of them. Glucose transporter type 1 (Glut1) is one of the metabolic biomarkers that is affected by several conditions such as stress, seizure, malignancy, and neurocognitive disorders. We studied the effect of SD, circadian reversed (R) and napping models on the Glut-1 expression level in the right and left amygdala.

Sixty-four Wistar rats were divided into eight groups as follow: Intact group that rats were placed in a cage without any intervention. In the sham group, rats were on the stable pedal of the SD apparatus (turn off). Experimental groups include total SD48, total SD48- (plus short nap), total SD48+ (plus long nap), R48, R48- (plus short nap), and R48+ (plus long nap). The Glut-1 expression level in the right and left amygdala were measured by western blotting.

Our findings demonstrated the significant effect of both SD for 48 hours and reversed circadian on the expression of Glut-1 from sham and intact groups. The long nap plus them could decrease the elevation of Glut-1 in the left amygdala. However, the short nap could not reduce this elevation of Glut-1.

Left amygdala is vulnerable to the fluctuation of hypothalamicpituitary-adrenal axis and stress. In other words, sleep disorders are affecting by Glut-1 as a metabolic biomarker in left amygdala alone.

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 the offspring of morphine-abstinent parent(s).

The offspring of various types of parental morphine-exposure were divided into 4 groups including offspring of healthy parents (CTL), offspring of paternal morphine-abstinence (PMA), offspring of maternal morphine-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 of association was measured using the Pearson correlation analysis.

A strong correlation was observed between pain and depressive-like behavior in female and male offspring of healthy parents. Moreover, in the male and female offspring of healthy parents and BMA, no significant correlation was observed between avoidance memory and pain behavior or depressive-like behavior. However, in the offspring of MMA, a strong correlation was observed between avoidance memory and depressive-like behavior.

The results of the study signified the importance of correlation analysis in addictive behavior. The results revealed that the pattern of correlation of the behavior of the offspring of MMA and PMA differed

The endogenous opioid system plays a basic role in pain suppression. The opiate analgesia is the most powerful and useful technique for reducing severe pain in many medical conditions. Transcranial direct current stimulation (tDCS) is a neuromodulator technique by which the cerebral cortex is stimulated with a weak and constant electrical current by the painless and non-invasive method.

In this experimental study, we investigated the effect of tDCS on morphine (1.25, 2.5 and 5 mg/kg)-induced pain responses; as we applied left prefrontal anodal stimulation with 0.2 mA intensity and 20 minutes.

our results revealed that the acute (One-time electrical stimulation 24 hours after the last administration of morphine three days) and subchronic (three times electrical stimulation; one session/day before each administration of morphine three days) left prefrontal anodal tDCS does not alter pain perception induced by different dose of morphine significantly.

Finally, our data indicated that there is no potentiated effect between acute tDCS or subchronic tDCS and morphine administration with tested parameters significantly.

Anxiety disorders, depression, and dementia are common in elderly, which may overlap in various neurological disorders. Stress can be a risk factor for long-term depression. It also suggests that depression plays a role in developing dementia. Amnesia is the most problem in dementia. Is amnesia a risk factor for depression? Considering the common underlying mechanisms for causing these disorders, the purpose of this study is to investigate the role of amnesia in developing depression.

Forty-eight wistar rats were divided into two main groups (sham-A and intervention-B) and four subgroups (Control-C, Chronic mild stress-D, hypoperfusion without stress-E, hypoperfusion with Mild stress-F). Permanent occlusion of bilateral common carotid artery was performed to induce cerebral hypoperfusion. Radial arm maze test and chronic unpredictable mild stress were used to evaluate amnesia and depression, respectively. Forced swim test was performed to assess severity of depression and finally we used neuronal count for evaluating cellular degeneration in the CA1 hippocampus region.

Cerebral hypoperfusion causes amnesia and significantly reduced the mean number of cells in the hippocampal CA1 area. Cerebral hypoperfusion and stress significantly increased the incidence of depression-like behavior.

Amnesia caused by cerebral hypoperfusion can increase the risk of depression, especially under stressful situations.

Physical exercise is known to have a positive effect on pain responses induced by stress, while chronic stress causes a negative effect on cognitive abilities. Depending on the type, duration, and intensity of the stressor, it can induce analgesia or hyperalgesia. Furthermore, the beneficial effects of traditional Chinese medicine MLC901 on stress processes have been reported. Here, the effects of MLC901 and moderate physical activity on pain response in restraint-stressed mice was investigated.

Male NMRI mice were used in this study and were restrained in plexiglass mesh restrainers for induction of chronic restraint stress. Treadmill exercise was carried out for moderated exercise, 5 days/week for 4 weeks. MLC901 was intraperitoneally administered in the experimental groups. The pain response of the adult NMRI mice was detected via the hot-plate test.

It was showed that intraperitoneal administration of MLC901 dose (0.4 but not 0.1 and 0.2 mg/kg; once/2 days; for 25 days) resulted in the decreased percentage of time in the hot plate, indicating hyperalgesia. Moreover, restraint stress for 3 but not 6 and 9 hours/day elicit hyperalgesia in mice. The data showed that subthreshold dose of MLC901 (0.1 mg/kg) reduced hyperalgesia in 3-day stressed mice. Moderate treadmill running (10 meters/min for 30 min/day, 5 days/ week) potentiated the effect of 6 and 9 days on pain (induced hyperalgesia) that was blocked by MLC901 (0.1 mg/kg).

Our findings indicated that subthreshold dose of MLC901 alone or when it associated with moderate exercise decreased hyperalgesia induced by stress, indicating the protective effect of MLC901.

Previous studies indicated that intensity level might be a determining factor in the beneficial or adverse effects of exercise on spatial memory. As intensive exercise appears to deteriorate learning and memory and recent reports have suggested that one-night sleep deprivation improves mood and neurogenesis in depressed patients for at least one day. The present study was designed to investigate the effect of REM sleep deprivation (REM-SD) on memory impairment induced by intense exercise. Animals had undergone an intense protocol (speed: 18 m/min and no tilt for the first week, the duration and treadmill tilt were increased progressively, 10 minutes and five degrees increased in each week) of treadmill for five days a week for five weeks then deprived of sleep for 24 hours using the water-filled multiple platforms. The level of mammalian Target of Rapamycin (mTOR) in the hippocampus and the prefrontal cortex (PFC) was assessed by Western blotting. Five weeks of intensive exercise and 24h REM-SD were decreased the level of mTOR expression; 24h REM-SD improved intensive exercise-associated decreases in the basal levels of mTOR. The present data suggested that REM-SD might be considered as a compensatory factor for a short time. In addition, increasing in the mTOR level could improve memory impairment-induced by intensive exercise

Physical exercise has positive effects on stress-induced pain response, while chronic stress persuades a negative effect on cognitive functions. Depending on the nature, duration and intensity of the stressor, it can repress pain (stress-induced analgesia) or exacerbate pain (stress-induced hyperalgesia). Furthermore, beneficial effects of Harmane on stress processes have been reported in rodents. This study aimed to investigate the effects of Harmane and moderate physical activity (associated or not) on pain response in restraint stressed mice.

Harmane was injected intraperitoneally at doses of 0.1, 0.3 and 0.6 mg/kg, every other day until 28 days, and pain response of the adult NMRI mice was detected using the hot-plate test

The results exhibited that Harmane, at all doses used, did not alter pain perception in mice; however, 3- but not 6 and 9-day restraint stress (3 hours per day) induced hyperalgesia per se. In addition, Harmane reduced hyperalgesia in 3-day stressed mice, while moderate treadmill running (10 m/min for 30 min/day, 5 day/week) caused hyperalgesia in 6- and 9-day stressed mice. Furthermore, the hyperalgesia induced by moderate treadmill running in 9-day stressed mice restored by Harmane.

The findings indicated that Harmane has a protective effect on hyperalgesia induced by stress per se or potentiated effect of moderate treadmill running in stressed mice.

Evidence report a bidirectional relationship between sleep deprivation (SD) and anxiety. Although many studies have confirmed the beneficial effects of alpha-lipoic acid (ALA) on central nervous system diseases, its effect on anxiogenic behaviors in SD condition has not been investigated. This study examines the effect of ALA on anxiety-related behaviors in SD rats.

Male Wistar rats were sleep deprived in the water box for 24 h, and then submitted to the elevated plus maze (EPM) for assessing the anxiety-related behaviors. Blood samples were obtained to assess the serum corticosterone level.

SD rats decreased the percentage time spent in the open arms (%OAT), showing an anxiogenic-like behavior. Pretreatment administration of ALA (35 mg/kg, three times, once in each day) prevented the anxiogenic-like behavior in the SD rats, suggesting the inhibiting effect of ALA on the anxiogenic response induced by SD. Moreover, ALA alone had no effect on the EPM parameters. Meanwhile, in none of the groups the open arm entry and locomotion altered compared to the control group. In addition, ALA prevented the increased corticosterone level in the blood of SD rats.

The results suggest that SD causes an anxiogenic-like behavior and increases corticosterone level. Pretreatment with ALA prevents the anxiogenic-like effects and decreased the corticosterone level in SD rats. Given the beneficial effect of ALA on improving the performance of rats in anxiety-related behavior in SD conditions, this compound might be future chance in order to decrease the disrupting effects of SD.