Association Between the (GT)26 Allele in the GRIN2A Promoter and Opioid Use Disorder.

Objective: N-methyl-D-aspartate (NMDA) receptors are involved in the development of opioid use disorder. The (GT)n polymorphism (rs3219790) in the NMDA receptor 2A subunit gene (GRIN2A) has been proposed as a potential biomarker for risk of opioid use disorder. In this case-control study, we investigated the association between rs3219790 and opioid use disorder in a Chinese Han population.

Ibudilast-Mediated Suppression of Neuronal TLR4 in the Prefrontal Cortex Mitigates Methamphetamine-Induced Neuroinflammation and Addictive Behaviours.

Methamphetamine (METH) use leads to addiction, neurotoxicity, and neuroinflammation. Ibudilast, a toll-like receptor 4 (TLR4) inhibitor, has been shown to reduce METH-induced neuroinflammation and self-administration, but its specific role in neuronal TLR4 signalling and associated behavioural outcomes remains poorly understood. This study examined Ibudilast's effects on METH reward, drug-seeking behaviour, and TLR4 signalling in a rat self-administration model.

Antidepressant effects of activation of infralimbic cortex via upregulation of BDNF and β-catenin in an estradiol withdrawal model.

Rationale: Clinical and preclinical studies have demonstrated that estradiol withdrawal after delivery is one of important factors involved in the pathogenesis of postpartum depression (PPD). The infralimbic cortex (IL) is related to anxiety and mood disorders. Whether IL neurons mediate PPD is still unclear.

tiRNA-Gly-GCC-001 in major depressive disorder: Promising diagnostic and therapeutic biomarker.

Background And Purpose: In major depressive disorder (MDD), exploration of biomarkers will be helpful in diagnosing the disorder as well as in choosing a treatment and predicting the treatment response. Currently, tRNA-derived small ribonucleic acids (tsRNAs) have been established as promising non-invasive biomarker candidates that may enable a more reliable diagnosis or monitoring of various diseases. Herein, we aimed to explore tsRNA expression together with functional activities in MDD development.

N-Isopropylbenzylamine-induced conditioned place preference, sensitization behaviour and self-administration in rodents.

N-Isopropylbenzylamine (N-ipb), a chain isomer of methamphetamine (METH) with similar physical properties, has been used as a substitute for METH in seized drug samples. However, the abuse potential of N-ipb remains unclear. Therefore, this study aimed to evaluate the abuse potential of N-ipb in comparison to METH, by using conditioned place preference (CPP), locomotor sensitization and intravenous self-administration tests.

Circulating plasma and exosome levels of the miR-320 family as a non-invasive biomarker for methamphetamine use disorder.

The neurobiological mechanism underlying methamphetamine (MA) use disorder was still unclear, and no specific biomarker exists for clinical diagnosis of this disorder. Recent studies have demonstrated that microRNAs (miRNAs) are involved in the pathological process of MA addiction. The purpose of this study was to identify novel miRNAs for the diagnosis biomarkers of MA user disorder.

Differential expression profiling of tRNA-Derived small RNAs and their potential roles in methamphetamine self-administered rats.

Transfer RNA-derived small RNAs (tsRNAs) are a novel class of short, non-coding RNAs that are closely associated with the pathogenesis of various diseases. Accumulating evidence has demonstrated their critical functional roles as regulatory factors in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress. However, the underlying mechanisms by which tRFs & tiRNAs affect methamphetamine-induced pathophysiological processes are largely unknown.

Association of GABA receptor delta subunit gene variations with increased risk of methamphetamine dependence.

Objective: Evidence reveals that γ-aminobutyric acid (GABA) receptors are involved in the development of methamphetamine (METH) dependence. The GABA receptor delta subunit gene (GABRD) might be a good candidate gene for METH dependence. In a case-control study, we investigated the association between the single nucleotide polymorphisms (SNPs) in GABRD and METH dependence in a Chinese Han population.

Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response.

Objective: Genetic variations can affect individual response to methadone maintenance treatment (MMT) for heroin addiction. The A118G variant (rs1799971) in the mu opioid receptor gene (OPRM1) is a potential candidate single nucleotide polymorphism (SNP) for personalized MMT. This study determined whether rs1799971 is related to MMT response or dose.

A comparison of reinforcing effectiveness and drug-seeking reinstatement of 2-fluorodeschloroketamine and ketamine in self-administered rats.

2-Fluorodeschloroketamine (2F-DCK), a structural analog of ketamine, has been reported to cause impaired consciousness, agitation, and hallucination in abuse cases. It has similar reinforcing and discriminative effects as ketamine. However, the reinforcing efficacy and drug-seeking reinstatement of this analog have not been clarified to date.

Corrigendum: Increased Expression of Plasma miRNA-320a and let-7b-5p in Heroin-Dependent Patients and Its Clinical Significance.

[This corrects the article DOI: 10.3389/fpsyt.2021.

Increased Expression of Plasma miRNA-320a and let-7b-5p in Heroin-Dependent Patients and Its Clinical Significance.

Heroin use disorder is a chronic and relapsing disease that induces persistent changes in the brain. The diagnoses of heroin use disorders are mainly based on subjective reports and no valid biomarkers available. Recent researches have revealed that circulating miRNAs are useful non-invasive biomarkers for diagnosing brain diseases such as Alzheimer's disease, multiple sclerosis, schizophrenia, and bipolar disorder.

Association study of genetic polymorphisms in with treatment response and dose in methadone maintenance treatment.

This study determined if gene variants in the GABA receptor delta subunit () are associated with treatment response and dose in methadone maintenance treatment (MMT) for heroin addiction.  A total of 286 MMT patients were recruited and divided into response and nonresponse groups based on retention time in therapy. A total of 177 responders were classified into low dose and high dose subgroups according to the stabilized methadone dose.

Role of nucleus accumbens microRNA-181a and MeCP2 in incubation of heroin craving in male rats.

Rationale: Epigenetic regulation has been implicated in the incubation of drug craving (the time-dependent increase in drug seeking after prolonged withdrawal from drug self-administration). There is little information available on the role of microRNAs in incubation of heroin craving.

Objective: This study aimed to investigate the roles and mechanisms of miR-181a and methyl CpG binding protein 2 (MeCP2) in the nucleus accumbens (NAc) in incubation of heroin seeking.

Association between GABA receptor delta subunit gene polymorphisms and heroin addiction.

Evidence suggests that γ-aminobutyric acid (GABA) receptors are involved in the development of drug dependence. Considering its exclusively extrasynaptic localization, GABA receptor delta subunit (GABRD) is likely involved in heroin addiction. The purpose of this study was to explore the association between the single nucleotide polymorphisms (SNPs) of GABRD and heroin addiction.

Akt and its phosphorylation in nucleus accumbens mediate heroin-seeking behavior induced by cues in rats.

Akt is initially identified as one of the downstream targets of phosphatidylinositol-3 kinase (PI3K) and is involved in morphine reward and tolerance. However, whether phospholyration of Akt (p-Akt) mediates heroin relapse remains unclear. Here, we aimed to explore the role of p-Akt in the nucleus accumbens (NAc) in cue-induced heroin-seeking behaviors after withdrawal.

Role of GABRD Gene Methylation in the Nucleus Accumbens in Heroin-Seeking Behavior in Rats.

Epigenetic modifications such as DNA methylation play important roles in regulating gene expression and may mediate neuroplasticity and lead to drug-induced aberrant behaviors. Although several brain regions and neurobiological mechanisms have been suggested to be involved in these processes, there is remarkably little known about the effects of DNA methylation on heroin-seeking behavior. Using a Sprague-Dawley rat model, we show that heroin self-administration resulted in gamma-aminobutyric acid type A receptor subunit delta (GABRD) gene hypomethylation, which was associated with transcriptional upregulation of GABRD in the nucleus accumbens (NAc).

Huperzine A inhibits heroin-seeking behaviors induced by cue or heroin priming in rats.

Cholinergic systems modulate dopaminergic function in brain pathways are thought to mediate heroin addiction. This study investigated whether huperzine A, an acetylcholinesterase inhibitor, has beneficial effects on heroin reward and heroin-seeking behavior. Rats were trained to self-administer heroin (50 μg/kg/infusion) under the fixed ratio 1 schedule for 14 days and then drug-seeking was extinguished for 10 days, after which reinstatement of drug-seeking was induced by conditioned cues or heroin priming.

Histone 3 lysine 9 acetylation of BRG1 in the medial prefrontal cortex is associated with heroin self‑administration in rats.

Heroin addiction is a chronic relapsing brain disorder with negative social consequences. Histone acetylation serves a role in drug‑induced behavior and neuroplasticity impairment. Brahma/SWI2‑related gene‑1 (BRG1) participates in cerebellar development, embryogenesis and transcriptional regulation of neuronal genes concurrent with histone modifications.

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.

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.

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.

Induction of S phase arrest and apoptosis by ethyl acetate extract from Tetrastigma hemsleyanum in human hepatoma HepG2 cells.

Tetrastigma hemsleyanum, a rare and endangered medicinal plant, has attracted much attention due to antitumor and immunomodulatory activities. In this study, the effect and mechanism of ethyl acetate extract from T. hemsleyanum (EET) on cell cycle and apoptosis in human hepatoma HepG2 cells were investigated.

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.

Positive association between--1021TT genotype of dopamine beta hydroxylase gene and progressive behavior of injection heroin users.

By balancing the ratios of dopamine and norepinephrine, dopamine beta hydroxylase (DBH) plays an important role in brain reward circuit that is involved with behavioral effects of heroin addiction. DBH -1021C/T (rs1611115) is a functional variant with strong correlation with plasma DBH activity and several nerval and psychic disorders. In the present study, we have collected 333 male cases with heroin addiction and 200 male healthy controls to explore the role of -1021C/T in heroin addiction.