Main problems experienced by the neighbors of open drug scenes, Tehran, Iran: a mixed-method study.

BACKGROUND: Despite law enforcement and health interventions, open drug scenes have led to problems in many countries. The problems are, however, insufficiently explored. There are different types of drug scenes in Iran. This study aimed to explore the issues related to neighbors of one of the drug scenes in Tehran known as Farahzad. METHODS: Data were generated via semi-structured interviews in the first step of the current mixed-method study (2020-2021). Interviewees were people who use drugs (PWUDs), residents and business owners (N = 25). In the next step, a quantitative observation was conducted for eight days. The results were analyzed using conventional content analysis and descriptive statistics. RESULTS: The perceived problems were ambivalent attitudes about drug scene-related activities, violate of the territory of the self of the effected residents, and everyday concerns. The observation results indicated that men who use drugs are involved in drug scene-related activities more than women are. PWUDs try to hide their activities from the public view. Their efforts were considered "self-regulatory strategies" in the drug scene. CONCLUSIONS: Despite efforts of PWUDs to keep their activities invisible, drug scene-related issues are intolerable for neighbors. Neighbors and PWUDs have ambivalent attitudes. While they are concerned about the human rights of each other, drug scene-related activities have disturbed the neighbor's daily life and economic activities. Although law enforcement and harm reduction interventions reduce some of the problems, one of the approaches should be improving the coexistence between the neighbors and the residents of the drug scene to achieve broader and more sustainable compromises.

The potential protective effect of melatonin and N-acetylcysteine alone and in combination on opioid-induced testicular dysfunction and degeneration in rat.

Methadone (Met) is the most common treatment for opioid addiction. Although Met is effective for treatment of opioid dependence, sexual dysfunctions and infertility have been reported as a major problem in patients under Met treatment. The present study aimed to evaluate the effect of melatonin and N-acetylcysteine (N) on morphine and Met-induced oxidative stress, apoptosis, suppression of blood sexual hormones, impairment in sperm parameters, and sexual dysfunction. Adult male Wistar rats (n = 66) were randomly divided into 11 equal groups (n = 6) as follows: control, sham, morphine, Met, Met+N, Met+ melatonin, Met+melatonin+N, morphine+ Met, morphine+Met+ melatonin, morphine+Met+N, and morphine+Met+ melatonin+N groups. On day 56 post-treatment, the blood was collected from the tail and the serum levels of sex hormones were evaluated, then the rats were sacrificed, and their bilateral testes and epididymis were retrieved for histological, immunohistochemical, molecular, testicular tissue stress oxidative status, and sperm parameters assays. Exposure to morphine, Met, and shift of morphine to Met resulted in testicular degeneration that can be attributed to generating the stress oxidative-induced- apoptotic testicular cell death and impairing spermatogenesis. Melatonin and N alone and particularly, in combination with each other improved testicular degeneration, sex hormone suppression, and testicular function mediated by increasing the testicular antioxidant capacity and inhibition of the apoptosis pathway. It's suggested that oral administration of antioxidants may be an effective treatment for attenuating some opioid-related testicular dysfunction and degeneration.

Inflammatory, oxidative stress and cognitive functions in patients under maintenance treatment with methadone or buprenorphine and healthy subjects.

BACKGROUND: Methadone and buprenorphine which are widely used for opioid maintenance treatment can affect redox status and also brain functions. The present study aimed to compare inflammation, oxidative stress, and cognitive function in methadone maintenance patients (MMP), buprenorphine maintenance patients (BMP), and healthy participants. METHOD: Oxidative- antioxidant markers, inflammatory factors were investigated in MMP (n = 30), BMP (n = 30), and healthy participants (n = 30) by evaluating the ferritin, malondialdehyde (MDA), total antioxidant capacity (TAC), and also High-sensitivity C-reactive protein (hs-CRP). Also, executive function was evaluated using Wisconsin Card Sorting Test (WCST). FINDINGS: MMP and BMP showed impairment in executive function compared to the healthy participants. Both buprenorphine and methadone treatments induced oxidative stress. The ferritin level in BMP was significantly lower compared to MMP and healthy participants (P = 0.01). There was a significant difference between control and MMP and BMP (P > 0.0001) in terms of hs-CRP level. BMP had the highest and healthy participant's lowest MDA level (P < 0.001). The TAC levels in BMP were lower than in MMP (p = 0.002) and healthy participants (p = 0.001). Finally, executive function was significantly correlated with oxidative-antioxidant status. DISCUSSION: Both methadone and buprenorphine induced severe oxidative activity (especially buprenorphine) and cognitive deficits compared to healthy participants. Stress oxidative can affect normal brain activity and consequently cognitive functions. It's suggested that concomitant antioxidant administration with buprenorphine or methadone can potentially enhance their beneficial action by regulating blood redox status.

Synergistic effect of combined transcranial direct current stimulation and Matrix Model on the reduction of methamphetamine craving and improvement of cognitive functioning: a randomized sham-controlled study.

Background: Addiction is associated with decreased activity of the prefrontal networks, especially dorsolateral prefrontal cortex (DLPFC).Objective: This study examined the effectiveness of transcranial direct current stimulation (tDCS) over DLPFC in combination with Matrix Model psychotherapy in the alleviation of craving and cognitive improvement of participants with methamphetamine use disorder.Methods: In a randomized and sham-controlled trial, 60 male participants were assigned to Matrix psychotherapy only, sham tDCS plus Matrix, or active tDCS plus Matrix. Sixteen sessions of 20-min anodal (2 mA over F3 for targeting the left DLPFC) or sham tDCS along were administered in the outpatient setting. Pre- and post-intervention craving, executive functioning, and working memory were assessed using the Obsessive-Compulsive Drug Use Scale, Wisconsin Card Sorting Test, and Wechsler Memory Scale, respectively. One month following the interventions relapse was investigated by urine drug screen or interview.Results: In comparison with sham tDCS (n = 12) and Matrix psychotherapy only group (n = 13), the active tDCS group (n = 15) showed more reduction in craving (p<.05, η2 = .21). Auditory and visual memory (Wechsler) and true answers and false answers (WCST) significantly improved in the active tDCS group (η2 = .18, η2 = 12, η2 = 03, η2 = .02, respectively) but not in the other groups. Relapse rates did not significantly differ between groups (p = .17). A significant correlation was found between craving reduction and cognitive functioning in the active tDCS group.Conclusion: The combination of Matrix Model psychotherapy and tDCS may an effective therapy for cognitive improvement and craving in participants with methamphetamine use disorder.Clinical Trials Registry: This study was registered at the Iranian Registry of Clinical Trials (IRCT20161026030510N3).

Psychopathological and neuropsychological outcomes of deep brain stimulation for severe- treatment-resistant obsessive-compulsive disorder: An open-label case series.

OBJECTIVE: Deep brain stimulation (DBS) is considered a promising intervention for treatment-resistant obsessive-compulsive disorder (OCD). The present study describes the outcomes of the first DBS procedures for OCD in Iran. METHODS: Four women patients (age range, 25-35 years) with severe OCD meeting stringent criteria for refractoriness to treatment were selected by Psychosurgery Review Board. DBS electrodes were bilaterally implanted in the internal capsule and nucleus accumbens (NAc). Clinical and neuropsychological assessments were undertaken before and after implantation. The outcomes included Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Hamilton Anxiety Rating Scale (HAM-A), neuropsychological assessments including the Wisconsin Card Sorting Test, Wechsler Memory Scale, and adverse events. RESULTS: The baseline mean score of the Y-BOCS and HAM-A was 32 ± 6 and 23 ± 14 respectively and decreased to 26 ± 8 and 17 ± 9 after one-year implantation, showing a 19% improvement. Two patients were responders and showed a notable improvement. One patient's score declined 28%, who was not satisfied with DBS results, and one patient worsened under-stimulation. Improvements in the severity of anxiety and cognitive performance were consistent with OCD improvement, and the successfully treated patients showed improvement in anxiety and cognitive performance. No significant cognitive declines were seen. Two patients' suicidal ideation appeared after DBS as an important adverse event. CONCLUSION: Bilateral DBS of the internal capsule/NAc may be an effective and safe treatment for treatment-refractory OCD. However, there is a need to consider accessibility, high cost, cost-effectiveness, and standardized methodology in future research.

The relationship between serum brain-derived neurotrophic level and neurocognitive functions in chronic methamphetamine users.

Methamphetamine (METH) is a highly addictive psychostimulant with serious neurotoxic effects. Given evidence indicating that brain-derived neurotrophic factor (BDNF) is associated with addictive behaviors, this study aimed to investigate the serum level of BDNF and cognitive functions in chronic METH users and healthy participants. Thirty-seven chronic METH users and 37 healthy participants were recruited in this study. Cognitive functioning, including executive functions and working memory, were assessed using the Wisconsin Card Sorting Test (WCST) and Wechsler Memory Scale (WMS), respectively. The levels of serum BDNF were also examined using an enzyme-linked immunosorbent assay kit. METH users showed significant impairment in executive function and working memory compared to healthy participants. The serum BDNF concentrations of METH users were significantly higher than healthy participants (42 ± 13.34 ng/ml vs. 24 ± 7 ng/ml). BDNF concentration was significantly correlated with duration (r = 0.37, p = 0.02) and dose of METH use (r = 0.35, p = 0.02). Besides, the BDNF level was not associated with any subscales of WCST and WMS. These results provide further evidence regarding the role of BDNF in the pathophysiology of METH addiction. Besides, these findings suggest that increased BDNF level is not related to cognitive impairments in METH users.

The Relationship Between Brain Metabolites Alterations and Neuropsychological Deficits in Patients with Methamphetamine Use Disorder: A Proton Magnetic Resonance Spectroscopy Study.

INTRODUCTION: Chronic use of methamphetamine induces neuropsychological deficits and neurochemical changes in frontostriatal regions. This study aimed to examine the relationship between brain metabolites alterations in frontostriatal regions and neuropsychological deficits in patients with methamphetamine use disorder. METHOD: A total of 30 methamphetamine users and 20 control participants were selected and a battery of standardized executive function, attention, and memory tasks, including the Wisconsin Card Sorting Test, Stroop Test, and Wechsler Memory Scale, was administered to them. Proton-Magnetic resonance spectroscopy (H-MRS) of N-Acetylaspartate/Creatine (NAA/Cr), Choline/Creatine (Cho/Cr), and glutamate + glutamine/creatine (Glx/Cr) in dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and basal ganglia (BG) were also undertaken. RESULTS: Current findings indicated that there were significant differences between two groups in metabolite ratios including NAA/Cr, Cho/Cr, and Glx/Cr in three areas, except for Glx/Cr in BG. Moreover, compared to healthy controls, methamphetamine users showed poorer performance in all neuropsychological tests. Finally, a significant relationship was found between regional metabolites alterations, particularly in the ACC, and neuropsychological deficits in methamphetamine users. CONCLUSIONS: In addition to neurochemical changes and neuropsychological deficits in patients with methamphetamine use disorder, current results highlighted the relationship between these changes in DLPFC, ACC, and BG with cognitive deficits in methamphetamine users.

The interaction between sexual reward/ deprivation and the acquisition, extinction and reinstatement of morphine-seeking behavior.

Natural rewards and abused drugs affect the function of the common brain's reward system. Interaction between social and drug rewards can change the vulnerability to development of drug addiction. Here, we investigate the effects of sexual experience and sex deprivation on the acquisition, maintenance, and drug prime-induced reinstatement of morphine-seeking behavior in male mice using conditioned place preference (CPP). CPP induced with morphine (3, 5, 7 mg/kg, s.c. for 3 days) lasted for 10 days after cessation of morphine treatment and priming dose of morphine (2 mg/kg, s.c.) reinstated the extinguished CPP. In the post-test phase, sexually experienced animals showed a lower preference for morphine compared to sex-deprived males. In the extinction phase, sex deprivation shortened maintenance time compared to control animals. The preference for morphine in sexually experienced animals did not diminish by the seventeenth extinction day. In both groups, the priming injection of morphine after the extinction period could reinstate the extinguished morphine-induced CPP. Together, these data showed the interaction between sex and drug reward and that sexual behavior -a natural rewarding stimulus- can prolong, whereas sex deprivation can block the maintenance of morphine-seeking behaviors. Sexual experience may induce functional and morphological alterations in brain reward areas particularly the mesolimbic system similar to repeated exposure to abused drugs which can affect morphine-seeking behaviors.

Indicators of Drug-Related Community Impacts of Open Drug Scenes: A Scoping Review.

INTRODUCTION: Places where people deal and/or use drugs publicly are known as open drug scenes (ODSs). Drug-related community impacts (DRCIs) refer to drug-related issues that negatively influence public and individual health, communities, businesses, and recreational and public space enjoyment. There are no well-established criteria for identification of DRCIs. We therefore performed a scoping review of literature to determine DRCIs indicators associated with ODSs. METHODS: The review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRISMA-ScP). We searched English articles in PubMed, Scopus, Web of Science, and EMBASE databases from 1990 to 2021. The keywords were drug-related crime, drug-related offense, misconduct, social marginalization, homeless drug users, open drug scene, drug-related street disorder, public nuisance, and community impact. RESULTS: Sixty-four studies were identified. Twenty-five studies were included. Two studies (8%) were about drug-related public nuisance, 1 (4%) considered drug-related social problems, 2 (8%) focused on drug-related social disorder, and 18 studies (72%) discussed indicators of community impacts such as crime, drug-related litter, safety, noise, and drug use in public. Two studies (8%) included the frequency of drug use in ODSs. DISCUSSION: DRCI indicators are heterogenic, and various factors affect the indicators. The factors include social mores, political discourse, and historical approaches to dealing with and using drugs. Some societies do not tolerate the existence of ODSs. In contrast, many countries have adopted harm reduction programs to manage DRCIs. Identified DRCI indicators were drug using and dealing in public, drug-related litter, crime, drug-related loitering, street-based income generation activities, noise, and unsafety feelings in inhabitants. To solve the problems associated with DRCIs and to make a major change in ODSs, it is necessary to pay attention to the improvement of the economic conditions (e.g., employment opportunities), amendment (e.g., determine the limits of criminalization in drug use), and adoption of social policies (e.g., providing low-threshold and supportive services for homeless drug users).

Successful Use of Minocycline for the Treatment of Methamphetamine-Induced Psychosis and Cognitive Impairments: An Open-Label Case Series.

AIM: Methamphetamine-induced psychosis and neuropsychological impairments are common among patients with methamphetamine use disorder. Given some preclinical and clinical studies reporting potential effects of minocycline, a second-generation tetracycline, on correcting manifestations of drug addiction, this study aimed to examine the effectiveness of minocycline in attenuating psychotic symptoms and neuropsychological impairments in chronic methamphetamine users. METHOD: Five men with treatment-resistant methamphetamine use disorder and psychotic symptoms were selected using a convenience sampling method, and they were administered a daily dose of 200-mg minocycline for 8 weeks; within this period, psychiatric and neuropsychological assessments (including memory and executive functions) were carried out at the baseline, week 2, week 4, week 8, and 2-month follow-up. RESULTS: The findings showed that minocycline attenuated both positive (Cohen d = 0.63) and negative (Cohen d = 0.53) methamphetamine-induced psychotic symptoms and also improved patients' neuropsychological functions, particularly their auditory working memory (Cohen d = 0.45). CONCLUSIONS: These results provide promising evidence regarding the positive effects of minocycline as adjunctive pharmacotherapy for patients with methamphetamine use disorder. However, given that this was an open-label study, further research is warranted to draw a firm conclusion about the effectiveness of minocycline for methamphetamine-induced psychosis and neuropsychological deficits.

Comparison of psychological symptoms and cognitive functions in patients under maintenance treatment with methadone or buprenorphine, current opioid users and healthy subjects.

Methadone and buprenorphine can affect the psychological symptoms and cognitive functioning of substance users. This study aimed to compare psychological symptoms and neuropsychological functioning in methadone maintenance patients (MMP), buprenorphine maintenance patients (BMP), current opioid users, and healthy subjects. One hundred and twenty participants (30 in each group) matched for age, sex, and education completed the Symptom Checklist-90-Revised (SCL-90-R) and a battery of neuropsychological tests including the Wisconsin Card Sorting Test (WCST), Wechsler Memory Scale (WMS-IV), and Stroop Color-Word Test (SCWT) assessing executive functioning, working memory, and attention, respectively. Overall, opioid users showed more severe psychological symptoms compared to healthy subjects. MMP and BMP had intermediate scores in SCL-90-R subscales; however, BMP had fewer severe symptoms compared to the MMP group. In terms of cognitive functioning, healthy subjects and current users demonstrated the best and the worst performance, respectively. Also, BMP outperforms MMP on executive functions and attention. However, the MMP had a better performance in WMS (visual memory). Patients receiving maintenance treatment had fewer psychological symptoms and better cognitive performance compared to opioid users. BMP had a better profile in all psychological symptoms and better performance in executive functions and selective attention compared to the MMP suggesting buprenorphine may be a better choice for the treatment of opioid-dependent patients.

Minocycline induces the expression of intra-accumbal glutamate transporter-1 in the morphine-dependent rats.

Glial glutamate transporters (GLT-1) is responsible for glutamate homeostasis. GLT-1 expression and glutamate uptake can be affected by addictive drugs and can be used as a target in addiction pharmacotherapy. It has been shown that minocycline, an antibiotic with anti-inflammatory, and neuroprotective properties, can upregulate the expression of GLT-1. In the present study, in morphine-dependent rats, the effect of minocycline on expression of GLT-1 in nucleus accumbens was investigated by immunohistochemistry. The expression of GLT-1 significantly increased in minocycline treated animals. In line with other studies, our findings showed that restoring GLT-1 expression with minocycline might be considered as a potential target for correcting pre-clinical and clinical manifestations of drug addiction.

Drug-related community issues and the required interventions in open drug scenes in Tehran, Iran: a qualitative study protocol.

BACKGROUND AND OBJECTIVES: Many low-income and middle-income countries experience problems with open drug scenes and drug-related community issues (DRCIs). These experiences occur in settings with varying levels of health and law enforcement initiatives, and accordingly a range of approaches are implemented to curb the problem. Most of the published literature stems from Western and high-income societies. With this concern, the present study aims to describe a planned project to explore DRCIs in the open drug scenes of Tehran, including its typology, and predisposing and reinforcing factors. In addition, the study attempts to investigate the perceptions with respect to the required interventions and barriers to their accessibility. METHODS: To this end, the current study focuses on the Farahzad drug scene due to its structure and the difficult access to the scene by harm reduction providers. Data collection techniques encompass field observation, indepth interview and focus group discussion. Further, semistructured interviews are conducted with people who use drugs and other key informants who are engaged at this drug scene, including business, community, voluntary and statutory stakeholders, for an average of 90 min (average of 45 min for each part of the study). Furthermore, as a complementary method, field observation is performed regarding the themes of DRCIs at this scene. Then, focus group discussions are held to further describe the themes of DRCIs as well as to explore the required interventions, for an average of 90 min. Finally, the results are evaluated using qualitative content analysis. ETHICS AND DISSEMINATION: Ethical approval for the study was obtained from the Ethics Committee of Iran University of Medical Sciences, Iran. Additionally, participants are to provide written informed consent. The findings of the study are expected to play a role in promoting the current intervention.

Minocycline increases firing rates of accumbal neurons and modifies the effects of morphine on neuronal activity.

Accumulating evidence indicated that minocycline, a glial cell modulator, is able to modify a variety of morphine effects. Here, we investigated minocycline effects on electrical activity of nucleus accumbens (NAc) neurons using single unit recording in urethane-anesthetized rats. In addition, we investigated whether minocycline can modify the effects of morphine on NAc neural activity during reinstatement of morphine-seeking behavior. Minocycline increased the NAc firing activity in intact animals. Electrophysiological recording in morphine-treated animals was performed, following the acquisition of morphine-induced conditioned place preference (5 mg/kg, s.c., 3 days) and a drug-free extinction period. In acutely minocycline- treated animals, the neurons were recorded for 40 minutes following a single injection of either minocycline (50 µg/5 µl, i.c.v.) or saline. Then a priming dose of morphine (1 mg/kg, s.c.) was injected while the recording was continued for an additional 40 minutes. Minocycline significantly increased the firing rates of neurons and significantly modified morphine inhibitory effects on NAc neurons. In subchronically minocycline-treated groups, the rats were given daily injections of minocycline (50 µg/5 µl, i.c.v) during the extinction period. Then, on the reinstatement day, NAc neurons were recorded for 10 minutes, the priming dose of morphine was administered and the recording was continued for 45 minutes. Our results showed the failure of minocycline to significantly modify the inhibitory effects of morphine. In conclusion, our findings indicated that minocycline modifies morphine-induced decreases in the firing rates of NAc neurons in the reinstatement phase.

Functional roles of orexin/hypocretin receptors in reward circuit.

Since its first discovery in 1998, it has become clear that the orexinergic system plays an important role in regulating a number of functions including food, sex, social connections, and most prominently reward-related behaviors. Orexinergic neurons in the lateral hypothalamus project extensively to other brain areas, two most important of which are the ventral tegmental area and the nucleus accumbens that are involved in reward processing. In this review, we have presented the work in our laboratory along with the work of others and have discussed the possible functions we can infer from the research. We discuss the anatomy of the orexinergic system and its components followed by a presentation of other connected brain areas. The second part of this review discusses observed results from the morphine conditioned place preference test that sheds light on the possible role of the involved areas in reward processing. The complex circuits involved in reward processing are only beginning to be understood and we need to deepen our understanding regarding the nature of the interactions between all brain areas involved.

Administration of activated glial condition medium in the nucleus accumbens extended extinction and intensified reinstatement of methamphetamine-induced conditioned place preference.

Methamphetamine (METH) is a psychostimulant drug with significant abuse potential and neurotoxic effects. A high percentage of users relapse to use after detoxification and no effective medication has been developed for treatment of METH addiction. Developing evidences indicated the role of glial cells in drugs abused related phenomena. However, little is known about the role of these cells in the maintenance and reinstatement of METH-seeking behaviors. Therefore, the current study was conducted to clarify the role of glial cells in the maintenance and reinstatement of METH-induced conditioned place preference (CPP) in rats. Astrocyte condition medium (ACM) and neuroglia conditioned medium (NCM) are liquid mediums prepared from primary astrocyte and neuroglia cells. These mediums seem to contain many factors that release by glia cells. CPP was induced by systemic administration of METH (1mg/kg for 5days, s.c.). Following the establishment of CPP, the rats were given daily bilateral injections (0.5µl/side) of either vehicle, ACM or NCM into the nucleus accumbens (NAc) and then were tested for the maintenance and reinstatement. Intra-NAc administration of ACM treated with METH, could extend the extinction period and also, intensified the magnitude of METH reinstatement. Furthermore, intra-accumbal administration of NCM treated with METH notably delayed the extinction period by four days and significantly increased the magnitude of CPP score in the reinstatement phase compared to the post-test phase. Collectively, these findings suggested that activation of glial cells may be involved in the maintenance and reinstatement of METH-seeking behaviors. It provides new evidence that glia cells might be considered as a potential target for the treatment of METH addiction.

Administration of the glial cell modulator, minocycline, in the nucleus accumbens attenuated the maintenance and reinstatement of morphine-seeking behavior.

Relapse to drug use is one of the most difficult clinical problems in treating addiction. Glial activation has been linked with the drug abuse, and the glia modulators such as minocycline can modulate the drug abuse effects. The aim of the present study was to determine whether minocycline could attenuate the maintenance and reinstatement of morphine. Conditioned place preference (CPP) was induced by subcutaneous injection of morphine (5 mg/kg) for 3 days. Following the acquisition of the CPP, the rats were given daily bilateral intra-NAc injections of either minocycline (1, 5, and 10 µg/0.5 µL) or saline (0.5 µL). The animals were tested for conditioning score 60 min after each injection. To induce the reinstatement, a priming dose of morphine (1 mg/kg) was injected 1 day after the final extinction day. The morphine-induced CPP lasted for 7 days after cessation of morphine treatment. Our data revealed that a priming dose of morphine could reinstate the extinguished morphine-induced CPP. Daily intra-accumbal injection of minocycline during the extinction period blocked the maintenance of morphine CPP and also attenuated the priming-induced reinstatement. Our findings indicated that minocycline could facilitate the extinction and attenuate the reinstatement of morphine. These results provided new evidence that minocycline might be considered as a promising therapeutic agent for the treatment of several symptoms associated with morphine abuse.

Administration of the Glial Condition Medium in the Nucleus Accumbens Prolong Maintenance and Intensify Reinstatement of Morphine-Seeking Behavior.

Accumulating evidence suggested that glial cells are involved in synaptic plasticity and behavioral changes induced by drugs abuse. The role of these cells in maintenance and reinstatement of morphine (MRP) conditioned place preference (CPP) remains poorly characterized. The aim of present study was to investigate the direct role of glial cells in nucleus accumbens (NAc) in the maintenance and reinstatement of MRP-seeking behavior. CPP induced with injection of MRP (5 mg/kg, s.c. for 3 days), lasted for 7 days after cessation of MRP treatment and priming dose of MRP (1 mg/kg, s.c.) reinstated the extinguished MRP-induced CPP. The astrocyte-conditioned medium (ACM) and neuroglia conditioned medium (NCM) exposed to MRP (10 and 100 µM) have been microinjected into the NAc. Intra-NAc administration of ACM during extinction period failed to change the maintenance of MRP-CPP, but MRP 100-treated ACM could slightly increase the magnitude of reinstatement. In contrast to ACM, intra-NAc administration of MRP 100-treated NCM caused slower extinction by 3 days and significantly increased the magnitude of reinstatement. Our findings suggest the involvement of glial cells activation in the maintenance and reinstatement of MRP-seeking behaviors, and provides new evidence that these cells might be a potential target for the treatment of MRP addiction.

The electrical activity of hippocampal pyramidal neuron is subjected to descending control by the brain orexin/hypocretin system.

The hippocampus receives sparse orexinergic innervation from the lateral hypothalamus and expresses a high level of orexin receptor. The function of orexin receptor in the regulation of hippocampal neural activity has never been investigated. In this study, in vivo single unit recording was performed in urethane-anesthetized rats. After 15 min of baseline recording from pyramidal neuron within the CA1 region of the dorsal hippocampus, i.c.v. injection of orexin-A 0.5 nmol, SB334867 400 nmol, a selective orexin receptor 1 antagonist, saline, or DMSO, or microinjection of carbachol 250 nmol or saline into the ipsilateral lateral hypothalamus were performed using a Hamilton microsyringe, and the spontaneous firing activity continued to be recorded for 25 min. Results showed that orexin administration into the lateral cerebral ventricle excited 6 out of 8 neurons and inhibited 1 neuron. Chemical stimulation of the lateral hypothalamus by carbachol excited 9 out of 13 hippocampal neurons and inhibited 3 neurons. On the other hand, i.c.v. injection of the SB334867, caused reductions in the firing activity of 6 out of 10 neurons and increases in 4 additional neurons. It seems that orexin neurotransmission in the hippocampus mostly elicits an excitatory response, whereas blockade of orexin receptor has an inhibitory effect. Further studies need to be done to elucidate the underlying mechanism of orexin action on hippocampal neurons.

Minocycline, an antibiotic with inhibitory effect on microglial activation, attenuates the maintenance and reinstatement of methamphetamine-seeking behavior in rat.

Methamphetamine (METH) is a major criminal justice and public health problem. Repeated use of METH causes dependence in humans and there are currently no particular pharmacological treatments for METH addiction. Glial cell activation is linked with METH abuse and METH administration causes activation of these cells in many areas of the brain. Many studies have demonstrated that glial cell modulators can modulate drug abuse effects. In this study, we examined the effect of the putative microglial inhibitor, minocycline on maintenance and prime-induced reinstatement of METH seeking behavior using the conditioned place preference (CPP) paradigm. CPP induced with METH (1 mg/kg, i.p. for 3 days) lasted for 11 days after cessation of METH treatment and priming dose of METH (0.5 mg/kg, i.p.) reinstated the extinguished METH-induced CPP. Daily treatment of minocycline (40 mg/kg, i.p.) followed by establishment of CPP blocked the maintenance of METH-induced CPP and also could attenuate priming-induced reinstatement. Furthermore, daily bilateral intra-accumbal injection of minocycline (10 and 20 µg/0.5 µl saline), during extinction period blocked the maintenance of METH CPP but just the highest dose of that could attenuate priming-induced reinstatement. We showed that minocycline administration during extinction period could facilitate extinction and maybe abolish the ability of drug-related cues evoke reinstatement, suggesting that minocycline might be considered as a promising therapeutic agent in preventing relapse in METH dependent individuals.