Effects of histone deacetylase inhibitor sodium butyrate on heroin seeking behavior in the nucleus accumbens in rats.

Histone acetylation and other modifications of the chromatin are important regulators of gene expression and may contribute to drug-induced behaviors and neuroplasticity. Inhibition of histone deacetylases (HDAC) activity results in the change of some drug-induced behaviors，however, relatively little is known about the effects of HDAC inhibitors on heroin-seeking behavior. In the present study, male rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 days, followed by 14 daily 2h extinction session in the operant chamber.

Association between genetic variations of NMDA receptor NR3 subfamily genes and heroin addiction in male Han Chinese.

Growing amounts of evidence suggest that N-Methyl-d-aspartate (NMDA) receptor mediated glutamate neurotransmission may be involved in the pathophysiology of drug dependence. The NMDA receptor consists of three subfamilies (NR1, NR2, and NR3). The ability of subunit NR3 to negatively modulate the NMDA receptor function makes it an attractive candidate gene of heroin addiction.

Ketamine abuse potential and use disorder.

Ketamine is a noncompetitive antagonist of N-methyl-d-asparate (NMDA) receptor and has been long used as an anesthetic agent in humans and veterinary medicine. The present article reviews the epidemiology, pharmacology, neurochemistry, and treatment of ketamine abuse. Ketamine has a unique mood controlling property and a number of studies have demonstrated a significant and rapid antidepressant effect of ketamine.

A significant association between BDNF promoter methylation and the risk of drug addiction.

As a member of the neurotrophic factor family, brain derived neurotrophic factor (BDNF) plays an important role in the survival and differentiation of neurons. The aim of our work was to evaluate the role of BDNF promoter methylation in drug addiction. A total of 60 drug abusers (30 heroin and 30 methylamphetamine addicts) and 52 healthy age- and gender-matched controls were recruited for the current case control study.

Activation of AMPA receptor in the infralimbic cortex facilitates extinction and attenuates the heroin-seeking behavior in rats.

Infralimbic cortex (IL) is proposed to suppress cocaine seeking after extinction, but whether the IL regulates the extinction and reinstatement of heroin-seeking behavior is unknown. To address this issue, the male SD rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 days, then the rats underwent 7 daily 2h extinction session in the operant chamber. The activation of IL by microinjection PEPA, an allosteric AMPA receptor potentiator into IL before each of extinction session facilitated the extinction responding after heroin self-administration, but did not alter the locomotor activity in an open field testing environment.

Environmental enrichment and abstinence attenuate ketamine-induced cardiac and renal toxicity.

The current study was designed to investigate the effect of abstinence in combination with environmental enrichment (EE) on cardiac and renal toxicity induced by 2 weeks of ketamine self-administration (SA) in rodents. In Experiment 1, one group of rats underwent ketamine SA for 14 days. In Experiment 2, the animals completed 2 weeks of ketamine SA followed by 2 and 4 weeks of abstinence.

Decrease of phosphorylated CREB and ERK in nucleus accumbens is associated with the incubation of heroin seeking induced by cues after withdrawal.

cAMP response element binding protein (CREB) signaling is involved in the heroin reward, but whether the CREB signaling is involved in the incubation of heroin-seeking remains unknown. Here we aim to explore the expression of p-CREB and the p-ERK, an upstream molecular of CREB, in the nucleus accumbens (NAc) in the incubation of heroin-seeking induced by cue after withdrawal. First, rats were trained to self-administer heroin for 14 days, and then assessed heroin-seeking induced by context cue (CC)or by conditioned cues (CS)after 1 or 14 d withdrawal.

Blockade of mGluR5 in the nucleus accumbens shell but not core attenuates heroin seeking behavior in rats.

Aim: Glutamatergic neurotransmission in the nucleus accumbens (NAc) is crucial for the relapse to heroin seeking. The aim of this study was to determine whether mGluR5 in the NAc core or shell involved in heroin seeking behavior in rats.

Methods: Male SD rats were self-administered heroin under a fixed-ratio 1 (FR1) reinforcement schedule for 14 d, and subsequently withdrawn for 2 weeks.

Continuous infusion versus intermittent bolus dosing of morphine: a comparison of analgesia, tolerance, and subsequent voluntary morphine intake.

Improved utilization of continuous or intermittent opioid administration in pain treatment necessitates a comparison of the antinociceptive effect and tolerance of these two treatment methods. More importantly, the effect of treatment method on subsequent opioid consumption has not been directly compared, although it is widely assumed that continuous opioid treatment may produce lower addictive liability relative to intermittent opioid treatment. In this study, we compared the antinociceptive effect and tolerance of morphine in rats that received repeated injection (10 mg/kg twice daily for 7 days) or continuous infusion (20 mg/kg daily for 7 days) subcutaneously and the self-administration of intravenous morphine in these rats after 7 days of withdrawal.

A heroin addiction severity-associated intronic single nucleotide polymorphism modulates alternative pre-mRNA splicing of the μ opioid receptor gene OPRM1 via hnRNPH interactions.

Single nucleotide polymorphisms (SNPs) in the OPRM1 gene have been associated with vulnerability to opioid dependence. The current study identifies an association of an intronic SNP (rs9479757) with the severity of heroin addiction among Han-Chinese male heroin addicts. Individual SNP analysis and haplotype-based analysis with additional SNPs in the OPRM1 locus showed that mild heroin addiction was associated with the AG genotype, whereas severe heroin addiction was associated with the GG genotype.

The phosphodiesterase-4 inhibitor rolipram attenuates heroin-seeking behavior induced by cues or heroin priming in rats.

Inhibition of phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes cyclic adenosine monophosphate (cAMP) increases intracellular cAMP/cAMP-response element binding protein (CREB) signaling. Activation of this signaling is considered as an important compensatory response that decreases motivational properties of drugs of abuse. However, it is not known whether PDE4 is involved in heroin seeking.

Long-term use of methamphetamine disrupts the menstrual cycles and hypothalamic-pituitary-ovarian axis.

Objectives: Long-term use of methamphetamine (MA) induces the neuron damage and leads to multiple neuropsychiatric disorders. However, the effect of MA on the female reproductive functions has not yet been evaluated. The objective of this study was to determine the prevalence of abnormal menstrual cycling in female MA users.

Low dose risperidone attenuates cue-induced but not heroin-induced reinstatement of heroin seeking in an animal model of relapse.

The aim of the present study was to investigate the effects of pretreatment with risperidone on heroin self-administration and heroin-seeking behaviour induced by cues and heroin priming. Rats were trained to self-administer heroin under a fixed ratio 1 schedule for 2 wk and nose-poke responding was extinguished for 10 d, after which reinstatement of drug seeking was induced by conditioned cues or heroin priming. Acute risperidone administration at doses 10-100 μg/kg potently and dose-dependently inhibited reinstatement of conditioned cue-induced heroin seeking; the minimum dose of inhibition was 30 μg/kg.

Negative moods correlate with craving in female methamphetamine users enrolled in compulsory detoxification.

Background: Methamphetamine (METH) use, especially in females, has become a growing public health concern in China. In this study, we aimed to characterize the factors that contributed to drug craving in female METH users under isolated compulsory detoxification. We characterized factors contributing to craving such as duration of detoxification, history of drug use and self-reported mood state.

Electroacupuncture suppresses discrete cue-evoked heroin-seeking and fos protein expression in the nucleus accumbens core in rats.

Relapse to drug seeking was studied using a rodent model of reinstatement induced by exposure to drug-related cues. Here, we used intravenous drug self-administration procedures in rats to further investigate the beneficial effects of electroacupuncture (EA) on heroin-seeking behavior in a reinstatement model of relapse. We trained Sprague-Dawley rats to nose-poke for i.

Galantamine attenuates the heroin seeking behaviors induced by cues after prolonged withdrawal in rats.

Background And Objective: Evidence shows that acetylcholinergic transmission in the ventral tegmental area (VTA) or nucleus accumbens (NAc) plays an important role in heroin-seeking induced by cues. Cholinergic modulation of VTA neurons arises from the lateral dorsal tegmental nucleus (LDT). The present studies investigated the effect of systemic or intra- LDT administration of galantamine, an inhibitor of acetylcholinesterase, on heroin-seeking induced by cues.

Differences in cigarette smoking behaviors among heroin inhalers versus heroin injectors.

Introduction: The high prevalence of cigarette smoking among heroin users has triggered many studies to explore possible interactions between cigarette smoking and heroin addiction; however, little is known about the relationship between cigarette smoking behaviors and routes of heroin administration. The present study provided the first examination of cigarette smoking status, motivation, and cigarette smoking cue reactivity among injecting or inhaling heroin users.

Methods: Forty-six heroin-dependent patients were recruited in the present study.

Vagus nerve stimulation inhibits heroin-seeking behavior induced by heroin priming or heroin-associated cues in rats.

Vagus nerve stimulation has been used for the treatment of neuropsychiatric disorders, such as epilepsy. However, little is known whether it is also effective for the treatment of heroin dependence, in particular for relapse to heroin seeking. In the present study, we investigated the effects of vagus nerve stimulation on reinstatement (relapse) of heroin-seeking behavior induced by heroin priming or heroin-associated cues.

Temporal changes of smoking status and motivation among Chinese heroin-dependent, methadone-maintained smokers.

Introduction: The rates of cigarette smoking remain extremely high in active heroin users and methadone-maintained patients. It remains undetermined whether smoking status and motivation would be differentially affected by heroin and methadone administration.

Methods: Heroin-dependent, methadone-maintained patients were recruited in the present studies.

Effects of training and withdrawal periods on heroin seeking induced by conditioned cue in an animal of model of relapse.

Rationale: A high incidence of relapse can be triggered by exposure to conditioned cues previously associated with heroin. Extended access to drug and withdrawal are thought to affect the motivation for drug seeking.

Objectives: The present study evaluated how different periods of training to self-administer heroin and different periods of withdrawal affected drug seeking.

Microinjection of M(5) muscarinic receptor antisense oligonucleotide into VTA inhibits FosB expression in the NAc and the hippocampus of heroin sensitized rats.

Objective: To investigate the effect of M(5) muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it's effect on the FosB expression in the nucleus accumbens (NAc) and the hippocampus in the heroin sensitized rats.

Methods: Locomotor activity was measured every 10 min for 1 h after subcutaneous injection of heroin. FosB expression was assayed by immunohistochemistry, and the antisense oligonucleotides (AS-ONs) targeting M(5) muscarinic receptor was transferred with the lipofectin.

Activation of the hypothalamus characterizes the response to acupuncture stimulation in heroin addicts.

Acupuncture stimulation elicited a composite of sensations termed deqi that is related to clinical efficacy. Neurobiological studies have identified the hypothalamus as an important component in mediating the deqi. Functional changes in hypothalamus persist after abstinence in addicts.

Role of acetylcholine transmission in nucleus accumbens and ventral tegmental area in heroin-seeking induced by conditioned cues.

The involvement of cholinergic transmission in heroin self-administration and the reinstatement of heroin-seeking was examined in rats trained to nose-poke for i.v. heroin.

SuperState: a computer program for the control of operant behavioral experimentation.

Operant behavioral researches require precise control of experimental devices for delivering stimuli and monitoring behavioral responses. The author developed a software solution named SuperState for controlling hardware devices and running reinforcement schedules. The Microsoft Windows compatible software was written by use of an object-oriented programming language Borland Delphi 5.