The SLC6A4 VNTR genotype determines transcription factor binding and epigenetic variation of this gene in response to cocaine in vitro.


:We demonstrated that the genotype of the variable number tandem repeats (VNTRs) in the linked polymorphic region (LPR) of the 5' promoter and in the intron 2 (Stin2) transcriptional regulatory domains of the serotonin transporter SLC6A4 gene determined its promoter interactions with transcription factors and co-activators in response to cocaine in the JAr cell line. The LPR variants contain 14 (short, s) or 16 (long, l) copies of a 22-23 bp repeat element, whereas the Stin2 VNTR exists as three variants containing 9, 10 or 12 copies of a 16-17 bp repeat. We observed a differential effect of cocaine on the association of the promoter with the transcription factor CTCF, which bound to both LPR alleles prior to cocaine exposure but only to the l-allele following exposure. Significantly, this differential effect of cocaine was correlated with the binding of the transcriptional regulator MeCP2 specifically to the s-allele and recruiting the histone deacetylase complex (HDAC). Concurrently, cocaine increased the association of positive histone marks over the SLC6A4 gene locus. At the Stin2 domain, we lost binding of the transcription factor YB-1, while CTCF remained bound. Our biochemical data are consistent with differential reporter gene activity directed by the individual or dual domains in response to cocaine in an Epstein-Barr virus-based episome model of stable transfections. These observations suggest that exposure of JAr cells to cocaine may result in differential binding of transcription factors and activators based on a specific genotype that might alter epigenetic parameters affecting gene expression after the initial challenge.


Addict Biol


Addiction biology


Vasiliou SA,Ali FR,Haddley K,Cardoso MC,Bubb VJ,Quinn JP




Has Abstract


2012-01-01 00:00:00












  • Effect of homozygous deletions at 22q13.1 on alcohol dependence severity and cue-elicited BOLD response in the precuneus.

    abstract::Copy number variations (CNVs) can alter the DNA sequence in blocks ranging from kilobases to megabases, involving more total nucleotides than single nucleotide polymorphisms. Yet, its impact in humans is far from fully understood. In this study, we investigate the relationship of genome-wide CNVs with brain function e...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Liu J,Calhoun VD,Chen J,Claus ED,Hutchison KE

    更新日期:2013-05-01 00:00:00

  • Long-term behavioral and pharmacodynamic effects of delta-9-tetrahydrocannabinol in female rats depend on ovarian hormone status.

    abstract::Abuse of Δ⁹-THC by females during adolescence may produce long-term deficits in complex behavioral processes such as learning, and these deficits may be affected by the presence of ovarian hormones. To assess this possibility, 40 injections of saline or 5.6 mg/kg of Δ⁹-THC were administered i.p. daily during adolescen...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Winsauer PJ,Daniel JM,Filipeanu CM,Leonard ST,Hulst JL,Rodgers SP,Lassen-Greene CL,Sutton JL

    更新日期:2011-01-01 00:00:00

  • Innate difference in the endocannabinoid signaling and its modulation by alcohol consumption in alcohol-preferring sP rats.

    abstract::The present study was undertaken to examine whether genetically predetermined differences in components of the endocannabinoid system were present in the brain of Sardinian alcohol-preferring (sP) and Sardinian alcohol-non-preferring (sNP) rats, a pair of rat lines selectively bred for opposite alcohol preference. The...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Vinod KY,Maccioni P,Garcia-Gutierrez MS,Femenia T,Xie S,Carai MA,Manzanares J,Cooper TB,Hungund BL,Colombo G

    更新日期:2012-01-01 00:00:00

  • Rat-strain dependent changes of dendritic and spine morphology in the hippocampus after cocaine self-administration.

    abstract::We previously showed that cocaine self-administration increases spine density in CA1 hippocampal neurons in Lewis (LEW) but not in Fischer 344 (F344) rats. Dendritic spine morphology is intimately related to its function. Thus, we conducted a 3D morphological analysis of CA1 dendrites and dendritic spines in these two...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Selvas A,Coria SM,Kastanauskaite A,Fernaud-Espinosa I,DeFelipe J,Ambrosio E,Miguéns M

    更新日期:2017-01-01 00:00:00

  • Neurological aspects of areca and betel chewing.

    abstract::Betel quid chewing has been claimed to produce a sense of well-being, euphoria, warm sensation of the body, sweating, salivation, palpitation, heightened alertness and increased capacity to work. These effects suggest that betel quid chewing affects predominantly the central and autonomic nervous systems. Several stud...

    journal_title:Addiction biology

    pub_type: 杂志文章,评审


    authors: Chu NS

    更新日期:2002-01-01 00:00:00

  • The cerebellum on cocaine: plasticity and metaplasticity.

    abstract::Despite the fact that several data have supported the involvement of the cerebellum in the functional alterations observed after prolonged cocaine use, this brain structure has been traditionally ignored and excluded from the circuitry affected by addictive drugs. In the present study, we investigated the effects of a...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Vazquez-Sanroman D,Leto K,Cerezo-Garcia M,Carbo-Gas M,Sanchis-Segura C,Carulli D,Rossi F,Miquel M

    更新日期:2015-09-01 00:00:00

  • Severity of dependence modulates smokers' neuronal cue reactivity and cigarette craving elicited by tobacco advertisement.

    abstract::Smoking-related cues elicit craving and mesocorticolimbic brain activation in smokers. Severity of nicotine dependence seems to moderate cue reactivity, but the direction and mechanisms of its influence remains unclear. Although tobacco control policies demand a ban on tobacco advertising, cue reactivity studies in sm...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Vollstädt-Klein S,Kobiella A,Bühler M,Graf C,Fehr C,Mann K,Smolka MN

    更新日期:2011-01-01 00:00:00

  • Age-related differences in working memory deficits during nicotine withdrawal.

    abstract::Nicotine withdrawal is associated with subtle working memory deficits that predict subsequent relapse. We examined the neural substrates underlying these processes in treatment-seeking smokers, and explored the moderating influence of age on abstinence-induced alterations in brain activity and performance. Sixty-three...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Falcone M,Wileyto EP,Ruparel K,Gerraty RT,LaPrate L,Detre JA,Gur R,Loughead J,Lerman C

    更新日期:2014-09-01 00:00:00

  • Abnormal gray matter volume and impulsivity in young adults with Internet gaming disorder.

    abstract::Reduced executive control is one of the central components of model on the development and maintenance of Internet gaming disorder (IGD). Among the various executive control problems, high impulsivity has consistently been associated with IGD. We performed voxel-based morphometric analysis with diffeomorphic anatomica...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Lee D,Namkoong K,Lee J,Jung YC

    更新日期:2018-09-01 00:00:00

  • Neural correlates of attentional bias for smoking cues: modulation by variance in the dopamine transporter gene.

    abstract::Cigarette-dependent smokers automatically and involuntarily orient attention toward smoking cues (SCs). This attentional bias is clinically significant, as it may contribute to relapse. Thus, identifying neural and genetic correlates of attentional bias is critical for improving interventions. Our previous studies sho...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Wetherill RR,Jagannathan K,Lohoff FW,Ehrman R,O'Brien CP,Childress AR,Franklin TR

    更新日期:2014-03-01 00:00:00

  • Strong increase in total delta-THC in cannabis preparations sold in Dutch coffee shops.

    abstract::The total concentration of THC has been monitored in cannabis preparations sold in Dutch coffee shops since 1999. This annual monitoring was issued by the Ministry of Health after reports of increased potency. The level of the main psychoactive compound, Delta9-tetrahydrocannabinol (THC), is measured in marijuana and ...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Pijlman FT,Rigter SM,Hoek J,Goldschmidt HM,Niesink RJ

    更新日期:2005-06-01 00:00:00

  • Respective influence of current alcohol consumption and duration of heavy drinking on brain morphological alterations in alcohol use disorder.

    abstract::Numerous studies have explored the morphological differences of the brain between subjects with alcohol use disorder (AUD) and control subjects, but very few have investigated the impact of the duration of alcohol use disorder (DAD) and current level of alcohol consumption (CAC) within AUD subjects using magnetic reso...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Rolland B,Dricot L,Creupelandt C,Maurage P,De Timary P

    更新日期:2020-03-01 00:00:00

  • Beyond cue reactivity: blunted brain responses to pleasant stimuli predict long-term smoking abstinence.

    abstract::Identifying addicts with higher risk of relapse would provide the opportunity to implement individualized interventions and increase cessation success rates. Unfortunately, the ability to predict the long-term success of drug cessation treatments continues to elude researchers. We tested whether brain responses to emo...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Versace F,Lam CY,Engelmann JM,Robinson JD,Minnix JA,Brown VL,Cinciripini PM

    更新日期:2012-11-01 00:00:00

  • Consilient research approaches in studying gene x environment interactions in alcohol research.

    abstract::This review article discusses the importance of identifying gene-environment interactions for understanding the etiology and course of alcohol use disorders and related conditions. A number of critical challenges are discussed, including the fact that there is no organizing typology for classifying different types of ...

    journal_title:Addiction biology

    pub_type: 杂志文章,评审


    authors: Sher KJ,Dick DM,Crabbe JC,Hutchison KE,O'Malley SS,Heath AC

    更新日期:2010-04-01 00:00:00

  • Role of peroxynitrite in methamphetamine-induced dopaminergic neurotoxicity and sensitization in mice.

    abstract::Abstract Methamphetamine (METH)-induced dopaminergic neurotoxicity is thought to be associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Recently, we have reported that copper/zinc(CuZn)-superoxide dismutase transgenic mice are resistant to METH-induced neurotoxicity. In...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Ali SF,Haung P,Itzhak Y

    更新日期:2000-07-01 00:00:00

  • Dietary yeast influences ethanol sedation in Drosophila via serotonergic neuron function.

    abstract::Abuse of alcohol is a major clinical problem with far-reaching health consequences. Understanding the environmental and genetic factors that contribute to alcohol-related behaviors is a potential gateway for developing novel therapeutic approaches for patients that abuse the drug. To this end, we have used Drosophila ...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Schmitt RE,Messick MR,Shell BC,Dunbar EK,Fang HF,Shelton KL,Venton BJ,Pletcher SD,Grotewiel M

    更新日期:2020-07-01 00:00:00

  • Preliminary evidence of different and clinically meaningful opioid withdrawal phenotypes.

    abstract::Opioid use disorder (OUD) is a public health crisis. Differences in opioid withdrawal severity that predict treatment outcome could facilitate the process of matching patients to treatments. This is a secondary analysis of a randomized controlled trial (RCT) that enrolled treatment seeking heroin-users (N = 89, males ...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Dunn KE,Weerts EM,Huhn AS,Schroeder JR,Tompkins DA,Bigelow GE,Strain EC

    更新日期:2020-01-01 00:00:00

  • Phosphorylated SNAP25 in the CA1 regulates morphine-associated contextual memory retrieval via increasing GluN2B-NMDAR surface localization.

    abstract::Although our previous studies have demonstrated both protein kinase C (PKC) and GluN2B-containing N-methyl-d-aspartate receptor (GluN2B-NMDAR) play crucial roles in morphine-associated learning and memory, the relationship between them remains unexplored. In this study, we validated the enhanced PKC and membrane GluN2...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Wang X,Liu Y,Jia M,Sun X,Wang N,Li Y,Cui C

    更新日期:2018-09-01 00:00:00

  • Posterior hippocampal regional cerebral blood flow predicts abstinence: a replication study.

    abstract::The posterior hippocampus (pHp) plays a major role in the processing and storage of drug-related cues and is linked to striatal-limbic brain circuits involved with craving and drug salience. We have recently reported that increased basal regional cerebral blood flow (rCBF) in a pHp loci, as measured by pseudo-continuo...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Adinoff B,Harris TS,Gu H,Stein EA

    更新日期:2017-05-01 00:00:00

  • Cue-induced nicotine-seeking behavior after withdrawal with or without extinction in rats.

    abstract::Exposure to smoking-associated environmental cues during smoke cessation elicits self-reported urge/craving to smoke, which precipitates relapse even after prolonged abstinence. Incubation of cue-induced cigarettes craving during abstinence has been observed in human smokers recently. The present studies assessed cue-...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Markou A,Li J,Tse K,Li X

    更新日期:2018-01-01 00:00:00

  • The role of reactive oxygen species in methamphetamine self-administration and dopamine release in the nucleus accumbens.

    abstract::Methamphetamine (METH) markedly increases dopamine (DA) release in the mesolimbic DA system, which plays an important role in mediating the reinforcing effects of METH. METH-induced DA release results in the formation of reactive oxygen species (ROS), leading to oxidative damage. We have recently reported that ROS are...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Jang EY,Yang CH,Hedges DM,Kim SP,Lee JY,Ekins TG,Garcia BT,Kim HY,Nelson AC,Kim NJ,Steffensen SC

    更新日期:2017-09-01 00:00:00

  • Demonstration of critical role of GRIN3A in nicotine dependence through both genetic association and molecular functional studies.

    abstract::Nicotine dependence (ND) is a chronic disease with catastrophic effects on individual and public health. The glutamate receptor subunit gene, ionotropic N-methyl-d-aspartate 3A (GRIN3A), encodes a crucial subunit of N-methyl-d-aspartate receptors (NMDARs), which play an essential role in synaptic plasticity in the bra...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Chen J,Liu Q,Fan R,Han H,Yang Z,Cui W,Song G,Li MD

    更新日期:2020-01-01 00:00:00

  • Operant model of frustrated expected reward in mice.

    abstract::One aspect of the addictive process that has not been thoroughly investigated is the consequence of the frustrated state occurring when the drug is not available. The present study aimed to validate a novel operant model of frustrated expected reward in mice. C57BL/6J mice were trained in operant conditioning maintain...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Burokas A,Gutiérrez-Cuesta J,Martín-García E,Maldonado R

    更新日期:2012-07-01 00:00:00

  • Antibodies to morphine as indicators of chronic morphine intoxication and impaired immune reactivity.

    abstract::Chronic morphine treatment of rats for 2 and 4 weeks led to an increase in morphine-binding cells in the spleen, despite the general reduction of mononuclear cell content in the spleen and thymus. Simultaneously, serum antibodies to morphine (AbM) in haemagglutination titres 1:20 and higher appeared in 50% and 80% of ...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Gamaleya N,Tronnikov S,Ulyanova L,Klimova S,Dmitrieva I

    更新日期:1996-01-01 00:00:00

  • Modification of pharmacokinetic and abuse-related effects of cocaine by human-derived cocaine hydrolase in monkeys.

    abstract::Although substantial research effort has focused on developing pharmacological treatments for cocaine abuse, no effective medications have been developed. Recent studies show that enzymes that metabolize cocaine in the periphery, forestalling its entry into the brain, can prevent cocaine toxicity and its behavioral ef...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Schindler CW,Justinova Z,Lafleur D,Woods D,Roschke V,Hallak H,Sklair-Tavron L,Redhi GH,Yasar S,Bergman J,Goldberg SR

    更新日期:2013-01-01 00:00:00

  • Male germline transmits fetal alcohol epigenetic marks for multiple generations: a review.

    abstract::Alcohol exposure during fetal and early postnatal development can lead to an increased incidence of later life adult-onset diseases. Examples include central nervous system dysfunction, depression, anxiety, hyperactivity, and an inability to deal with stressful situations, increased infection and cancer. Direct effect...

    journal_title:Addiction biology

    pub_type: 杂志文章,评审


    authors: Sarkar DK

    更新日期:2016-01-01 00:00:00

  • Long-term haloperidol treatment (but not risperidone) enhances addiction-related behaviors in mice: role of dopamine D2 receptors.

    abstract::The high prevalence of psychostimulant abuse observed in schizophrenic patients may be related to the development of mesolimbic dopaminergic supersensitivity (MDS) or nigrostriatal dopaminergic supersensitivity (NDS) in response to the chronic blockade of dopamine receptors produced by typical neuroleptic treatment. W...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Carvalho RC,Fukushiro DF,Helfer DC,Callegaro-Filho D,Trombin TF,Zanlorenci LH,Sanday L,Silva RH,Frussa-Filho R

    更新日期:2009-07-01 00:00:00

  • Neural correlates of tobacco cue reactivity predict duration to lapse and continuous abstinence in smoking cessation treatment.

    abstract::It has been hypothesized that neural reactivity to drug cues in certain limbic/paralimbic regions of the brain is an indicator of addiction severity and a marker for likelihood of success in treatment. To address this question, in the current study, 32 participants (44 percent female) completed a functional magnetic r...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Owens MM,MacKillop J,Gray JC,Beach SRH,Stein MD,Niaura RS,Sweet LH

    更新日期:2018-09-01 00:00:00

  • Effects of naltrexone plus topiramate on ethanol self-administration and tyrosine hydroxylase gene expression changes.

    abstract::The purpose of this study was to evaluate the effects of naltrexone (0.7 mg/kg) and/or topiramate (25 mg/kg) on ethanol consumption and the motivation to drink in an oral-operant conditioning paradigm in C57BL/6 mice. Subsequent real-time polymerase chain reaction (PCR) experiments were performed to analyze gene expre...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Navarrete F,Rubio G,Manzanares J

    更新日期:2014-09-01 00:00:00

  • Adolescent binge-ethanol accelerates cognitive impairment and β-amyloid production and dysregulates endocannabinoid signaling in the hippocampus of APP/PSE mice.

    abstract::Previous research in rodents suggests that the long-term neurobehavioral disturbances induced by chronic ethanol (EtOH) exposure could be due to endocannabinoid system (ECS) alterations. Moreover, ECS failure has been proposed to mediate the cognitive impairment and β-amyloid production in Alzheimer disease (AD). Thus...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Ledesma JC,Rodríguez-Arias M,Gavito AL,Sánchez-Pérez AM,Viña J,Medina Vera D,Rodríguez de Fonseca F,Miñarro J

    更新日期:2021-01-01 00:00:00