Abstract:
: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.
journal_name
Addict Bioljournal_title
Addiction biologyauthors
Vasiliou SA,Ali FR,Haddley K,Cardoso MC,Bubb VJ,Quinn JPdoi
10.1111/j.1369-1600.2010.00288.xsubject
Has Abstractpub_date
2012-01-01 00:00:00pages
156-70issue
1eissn
1355-6215issn
1369-1600journal_volume
17pub_type
杂志文章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
doi:10.1111/j.1369-1600.2011.00393.x
更新日期:2013-05-01 00:00:00
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
doi:10.1111/j.1369-1600.2010.00227.x
更新日期:2011-01-01 00:00:00
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
doi:10.1111/j.1369-1600.2010.00299.x
更新日期:2012-01-01 00:00:00
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
doi:10.1111/adb.12294
更新日期:2017-01-01 00:00:00
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
doi:10.1080/13556210120091473
更新日期:2002-01-01 00:00:00
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
doi:10.1111/adb.12223
更新日期:2015-09-01 00:00:00
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
doi:10.1111/j.1369-1600.2010.00207.x
更新日期:2011-01-01 00:00:00
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
doi:10.1111/adb.12051
更新日期:2014-09-01 00:00:00
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
doi:10.1111/adb.12552
更新日期:2018-09-01 00:00:00
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
doi:10.1111/j.1369-1600.2012.00507.x
更新日期:2014-03-01 00:00:00
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
doi:10.1080/13556210500123217
更新日期:2005-06-01 00:00:00
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
doi:10.1111/adb.12751
更新日期:2020-03-01 00:00:00
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
doi:10.1111/j.1369-1600.2011.00372.x
更新日期:2012-11-01 00:00:00
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
doi:10.1111/j.1369-1600.2009.00189.x
更新日期:2010-04-01 00:00:00
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
doi:10.1111/j.1369-1600.2000.tb00200.x
更新日期:2000-07-01 00:00:00
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
doi:10.1111/adb.12779
更新日期:2020-07-01 00:00:00
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
doi:10.1111/adb.12680
更新日期:2020-01-01 00:00:00
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
doi:10.1111/adb.12558
更新日期:2018-09-01 00:00:00
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
doi:10.1111/adb.12361
更新日期:2017-05-01 00:00:00
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
doi:10.1111/adb.12480
更新日期:2018-01-01 00:00:00
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
doi:10.1111/adb.12419
更新日期:2017-09-01 00:00:00
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
doi:10.1111/adb.12718
更新日期:2020-01-01 00:00:00
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
doi:10.1111/j.1369-1600.2011.00423.x
更新日期:2012-07-01 00:00:00
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
doi:10.1080/1355621961000125046
更新日期:1996-01-01 00:00:00
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
doi:10.1111/j.1369-1600.2011.00424.x
更新日期:2013-01-01 00:00:00
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
doi:10.1111/adb.12186
更新日期:2016-01-01 00:00:00
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
doi:10.1111/j.1369-1600.2008.00145.x
更新日期:2009-07-01 00:00:00
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
doi:10.1111/adb.12549
更新日期:2018-09-01 00:00:00
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
doi:10.1111/adb.12058
更新日期:2014-09-01 00:00:00
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
doi:10.1111/adb.12883
更新日期:2021-01-01 00:00:00