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












  • 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

  • Prolonged withdrawal from cocaine self-administration affects prefrontal cortex- and basolateral amygdala-nucleus accumbens core circuits but not accumbens GABAergic local interneurons.

    abstract::Withdrawal from extended-access cocaine self-administration leads to progressive intensification ('incubation') of cocaine craving. After prolonged withdrawal (1-2 months), when craving is high, expression of incubation depends on strengthening of excitatory inputs to medium spiny neurons (MSN) of the nucleus accumben...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Purgianto A,Weinfeld ME,Wolf ME

    更新日期:2017-11-01 00:00:00

  • Activation of the ventral and dorsal striatum during cue reactivity in Internet gaming disorder.

    abstract::Studies conducted in drug addiction suggest a transition in processing of drug-related cues from the ventral to the dorsal component of the striatum. However, this process has not been studied in a behavioral addiction. Assessment of this process in a non-drug addiction can provide insight into the pathophysiology of ...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Liu L,Yip SW,Zhang JT,Wang LJ,Shen ZJ,Liu B,Ma SS,Yao YW,Fang XY

    更新日期:2017-05-01 00:00:00

  • Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus.

    abstract::Recent preclinical evidence indicates that the neuropeptide oxytocin may have potential in the treatment of drug dependence and drug withdrawal. Oxytocin reduces methamphetamine self-administration, conditioned place preference and hyperactivity in rodents. However, it is unclear how oxytocin acts in the brain to prod...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Carson DS,Hunt GE,Guastella AJ,Barber L,Cornish JL,Arnold JC,Boucher AA,McGregor IS

    更新日期:2010-10-01 00:00:00

  • Blood naltrexone and 6-beta-naltrexol levels following naltrexone implant: comparing two naltrexone implants.

    abstract::The aim of this study was to profile and compare blood naltrexone and 6-beta-naltrexol levels with time following treatment with two sustained-release naltrexone preparations produced by GoMedical Industries, Australia at a community heroin treatment clinic in Perth, Western Australia. A sample of 10 patients who each...

    journal_title:Addiction biology

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Hulse GK,Arnold-Reed DE,O'Neil G,Chan CT,Hansson R,O'Neil P

    更新日期:2004-03-01 00:00:00

  • Abnormal white matter structural networks characterize heroin-dependent individuals: a network analysis.

    abstract::Neuroimaging studies suggested that drug addiction is linked to abnormal brain functional connectivity. However, little is known about the alteration of brain white matter (WM) connectivity in addictive drug users and nearly no study has been performed to examine the alterations of brain WM connectivity in heroin-depe...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Zhang R,Jiang G,Tian J,Qiu Y,Wen X,Zalesky A,Li M,Ma X,Wang J,Li S,Wang T,Li C,Huang R

    更新日期:2016-05-01 00:00:00

  • Rapamycin attenuates the expression of cocaine-induced place preference and behavioral sensitization.

    abstract::The mammalian target of rapamycin (mTOR) is a serine-threonine kinase that controls global protein synthesis, in part, by modulating translation initiation, a rate-limiting step for many mRNAs. Previous studies implicate mTOR in regulating stimulant-induced sensitization and antidepressive-like behavior in rodents, as...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Bailey J,Ma D,Szumlinski KK

    更新日期:2012-03-01 00:00:00

  • Working memory and salivary brain-derived neurotrophic factor as developmental predictors of cocaine seeking in male and female rats.

    abstract::Poor working memory is linked to future risk-taking behaviors. Lifelong risk of habitual drug use is highest in individuals who initiate use in early adolescence. We sought to determine in rats whether juvenile traits, specifically poor working memory and low salivary brain-derived neurotrophic factor (BDNF), are rela...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Jordan CJ,Andersen SL

    更新日期:2018-05-01 00:00:00

  • Characterization of hangover following intravenous alcohol exposure in social drinkers: methodological and clinical implications.

    abstract::Hangover refers to the cluster of physiological and behavioral symptoms that occur following the end of a drinking episode. While hangover has been studied after the typical oral consumption of alcohol, the occurrence of hangover following intravenous (IV) alcohol administration in human laboratory studies has not bee...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Vatsalya V,Stangl BL,Schmidt VY,Ramchandani VA

    更新日期:2018-01-01 00:00:00

  • Abstinent chronic crack-cocaine and crackcocaine/alcohol abusers evidence normal hippocampal volumes on MRI despite persistent cognitive impairments.

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    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: DI Sclafani V,Truran DL,Bloomer C,Tolou-Shams M,Clark HW,Norman D,Hannauer D,Fein G

    更新日期:1998-07-01 00:00:00

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    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Garrabou G,Hernàndez AS,Catalán García M,Morén C,Tobías E,Córdoba S,López M,Figueras F,Grau JM,Cardellach F

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    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Stefanik MT,Moussawi K,Kupchik YM,Smith KC,Miller RL,Huff ML,Deisseroth K,Kalivas PW,LaLumiere RT

    更新日期:2013-01-01 00:00:00

  • OPRM1 genotype interacts with serotonin system dysfunction to predict alcohol-heightened aggression in primates.

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    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Driscoll CA,Lindell SG,Schwandt ML,Suomi SJ,Higley JD,Heilig M,Barr CS

    更新日期:2017-11-01 00:00:00

  • The dopamine D3 receptor partial agonist CJB090 and antagonist PG01037 decrease progressive ratio responding for methamphetamine in rats with extended-access.

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    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Orio L,Wee S,Newman AH,Pulvirenti L,Koob GF

    更新日期:2010-07-01 00:00:00

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    journal_title:Addiction biology

    pub_type: 杂志文章


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  • Gender differences in the effects of cannabidiol on ethanol binge drinking in mice.

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    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Viudez-Martínez A,García-Gutiérrez MS,Manzanares J

    更新日期:2020-05-01 00:00:00

  • An acetylcholine-dopamine interaction in the nucleus accumbens and its involvement in ethanol's dopamine-releasing effect.

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    journal_title:Addiction biology

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  • Buprenorphine and carbamazepine as a treatment for detoxification of opiate addicts with multiple drug misuse: a pilot study.

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    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Schneider U,Paetzold W,Eronat V,Huber TJ,Seifert J,Wiese B,Emrich HM

    更新日期:2000-01-01 00:00:00

  • Rev-erbα modulates the hypothalamic orexinergic system to influence pleasurable feeding behaviour in mice.

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    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Feillet CA,Bainier C,Mateo M,Blancas-Velázquez A,Salaberry NL,Ripperger JA,Albrecht U,Mendoza J

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

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    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

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    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Zhang JT,Yao YW,Li CS,Zang YF,Shen ZJ,Liu L,Wang LJ,Liu B,Fang XY

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  • The pharmacology of psilocybin.

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    journal_title:Addiction biology

    pub_type: 杂志文章,评审


    authors: Passie T,Seifert J,Schneider U,Emrich HM

    更新日期:2002-10-01 00:00:00

  • Intermittent self-administration of fentanyl induces a multifaceted addiction state associated with persistent changes in the orexin system.

    abstract::The orexin (hypocretin) system plays a critical role in motivated drug taking. Cocaine self-administration with the intermittent access (IntA) procedure produces a robust addiction-like state that is orexin-dependent. Here, we sought to determine the role of the orexin system in opioid addiction using IntA self-admini...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Fragale JE,James MH,Aston-Jones G

    更新日期:2020-08-14 00:00:00

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    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

  • Attentional bias in alcohol-dependent patients: the role of chronicity and executive functioning.

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    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Loeber S,Vollstädt-Klein S,von der Goltz C,Flor H,Mann K,Kiefer F

    更新日期:2009-04-01 00:00:00

  • A study of hepatobiliary function in chronic heroin smokers.

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    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Banerjee D,Sarkar NK

    更新日期:1996-01-01 00:00:00

  • Enkephalin is essential for the molecular and behavioral expression of cocaine sensitization.

    abstract::Behavioral sensitization to cocaine is associated to neuroadaptations that contribute to addiction. Enkephalin is highly expressed in mesocorticolimbic areas associated with cocaine-induced sensitization; however, their influence on cocaine-dependent behavioral and neuronal plasticity has not been explained. In this s...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Mongi-Bragato B,Zamponi E,García-Keller C,Assis MA,Virgolini MB,Mascó DH,Zimmer A,Cancela LM

    更新日期:2016-03-01 00:00:00

  • Genetic differences in the modulation of accumbal glutamate and γ-amino butyric acid levels after cocaine-induced reinstatement.

    abstract::The Lewis (LEW) and Fischer 344 (F344) inbred rat strains are frequently used to study the role of genetic factors in vulnerability to drug addiction and relapse. Glutamate and γ-amino butyric acid (GABA) transmission are significantly altered after cocaine-induced reinstatement, although whether LEW and F344 rats dif...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Miguéns M,Botreau F,Olías O,Del Olmo N,Coria SM,Higuera-Matas A,Ambrosio E

    更新日期:2013-07-01 00:00:00

  • Neurological, nutritional and alcohol consumption factors underlie cognitive and motor deficits in chronic alcoholism.

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    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Fama R,Le Berre AP,Hardcastle C,Sassoon SA,Pfefferbaum A,Sullivan EV,Zahr NM

    更新日期:2019-03-01 00:00:00

  • Involving the cerebellum in cocaine-induced memory: pattern of cFos expression in mice trained to acquire conditioned preference for cocaine.

    abstract::Because of its primary role in drug-seeking, consumption and addictive behaviour, there is a growing interest in identifying the neural circuits and molecular mechanisms underlying the formation, maintenance and retrieval of drug-related memories. Human studies, which focused on neuronal systems that store and control...

    journal_title:Addiction biology

    pub_type: 杂志文章


    authors: Carbo-Gas M,Vazquez-Sanroman D,Aguirre-Manzo L,Coria-Avila GA,Manzo J,Sanchis-Segura C,Miquel M

    更新日期:2014-01-01 00:00:00