The absence of VGLUT3 predisposes to cocaine abuse by increasing dopamine and glutamate signaling in the nucleus accumbens.

Abstract:

:Tonically active cholinergic interneurons (TANs) from the nucleus accumbens (NAc) are centrally involved in reward behavior. TANs express a vesicular glutamate transporter referred to as VGLUT3 and thus use both acetylcholine and glutamate as neurotransmitters. The respective roles of each transmitter in the regulation of reward and addiction are still unknown. In this study, we showed that disruption of the gene that encodes VGLUT3 (Slc17a8) markedly increased cocaine self-administration in mice. Concomitantly, the amount of dopamine (DA) release was strongly augmented in the NAc of VGLUT3(-/-) mice because of a lack of signaling by metabotropic glutamate receptors. Furthermore, dendritic spines and glutamatergic synaptic transmission on medium spiny neurons were increased in the NAc of VGLUT3(-/-) mice. Increased DA and glutamate signaling in the NAc are hallmarks of addiction. Our study shows that TANs use glutamate to reduce DA release and decrease reinforcing properties of cocaine in mice. Interestingly, we also observed an increased frequency of rare variations in SLC17A8 in a cohort of severe drug abusers compared with controls. Our findings identify VGLUT3 as an unexpected regulator of drug abuse.

journal_name

Mol Psychiatry

journal_title

Molecular psychiatry

authors

Sakae DY,Marti F,Lecca S,Vorspan F,Martín-García E,Morel LJ,Henrion A,Gutiérrez-Cuesta J,Besnard A,Heck N,Herzog E,Bolte S,Prado VF,Prado MA,Bellivier F,Eap CB,Crettol S,Vanhoutte P,Caboche J,Gratton A,Moquin L,

doi

10.1038/mp.2015.104

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

1448-59

issue

11

eissn

1359-4184

issn

1476-5578

pii

mp2015104

journal_volume

20

pub_type

杂志文章
  • High throughput fluorescent CE-SSCP SNP genotyping.

    abstract::Large numbers of single nucleotide polymorphisms (SNPs) are being identified by several laboratories for the purpose of developing dense genetic maps. Single-strand conformation polymorphism (SSCP) analysis has been widely used as a method for detecting novel sequence variations in PCR products. Differences in migrati...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/sj.mp.4000564

    authors: Gonen D,Veenstra-VanderWeele J,Yang Z,Leventhal B,Cook EH Jr

    更新日期:1999-07-01 00:00:00

  • TrkB receptor cleavage by delta-secretase abolishes its phosphorylation of APP, aggravating Alzheimer's disease pathologies.

    abstract::Neurotrophins promote neuronal survival and synaptic plasticity via activating the tropomyosin receptor kinases. BDNF and its high-affinity receptor TrkB are reduced in Alzheimer's disease (AD), contributing to progressive cognitive decline. However, how the signaling mediates AD pathologies remains incompletely under...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/s41380-020-00863-8

    authors: Xia Y,Wang ZH,Liu P,Edgington-Mitchell L,Liu X,Wang XC,Ye K

    更新日期:2020-08-11 00:00:00

  • PS1 FAD mutants decrease ephrinB2-regulated angiogenic functions, ischemia-induced brain neovascularization and neuronal survival.

    abstract::Microvascular pathology and ischemic lesions contribute substantially to neuronal dysfunction and loss that lead to Alzheimer disease (AD). To facilitate recovery, the brain stimulates neovascularization of damaged tissue via sprouting angiogenesis, a process regulated by endothelial cell (EC) sprouting and the EphB4/...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/s41380-020-0812-7

    authors: Yoon Y,Voloudakis G,Doran N,Zhang E,Dimovasili C,Chen L,Shao Z,Darmanis S,Tang C,Tang J,Wang VX,Hof PR,Robakis NK,Georgakopoulos A

    更新日期:2020-06-15 00:00:00

  • Predicting educational achievement from DNA.

    abstract::This corrects the article DOI: 10.1038/mp.2016.107. ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/mp.2017.203

    authors: Selzam S,Krapohl E,von Stumm S,O'Reilly PF,Rimfeld K,Kovas Y,Dale PS,Lee JJ,Plomin R

    更新日期:2018-01-01 00:00:00

  • Association of a corticotropin-releasing hormone receptor 1 haplotype and antidepressant treatment response in Mexican-Americans.

    abstract::There are well-replicated, independent lines of evidence supporting a role for corticotropin-releasing hormone (CRH) in the pathophysiology of depression. CRH receptor 1 (CRHR1), which we first mapped in the brain in 1994, has been implicated in the treatment of depression and anxiety. We studied the association of CR...

    journal_title:Molecular psychiatry

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1038/sj.mp.4001587

    authors: Licinio J,O'Kirwan F,Irizarry K,Merriman B,Thakur S,Jepson R,Lake S,Tantisira KG,Weiss ST,Wong ML

    更新日期:2004-12-01 00:00:00

  • FKBP51 inhibits GSK3β and augments the effects of distinct psychotropic medications.

    abstract::Psychotropic medications target glycogen synthase kinase 3β (GSK3β), but the functional integration with other factors relevant for drug efficacy is poorly understood. We discovered that the suggested psychiatric risk factor FK506 binding protein 51 (FKBP51) increases phosphorylation of GSK3β at serine 9 (pGSK3β(S9))....

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2015.38

    authors: Gassen NC,Hartmann J,Zannas AS,Kretzschmar A,Zschocke J,Maccarrone G,Hafner K,Zellner A,Kollmannsberger LK,Wagner KV,Mehta D,Kloiber S,Turck CW,Lucae S,Chrousos GP,Holsboer F,Binder EB,Ising M,Schmidt MV,Rein T

    更新日期:2016-02-01 00:00:00

  • Environmental enrichment or selective activation of parvalbumin-expressing interneurons ameliorates synaptic and behavioral deficits in animal models with schizophrenia-like behaviors during adolescence.

    abstract::Synaptic deficit-induced excitation and inhibition (E/I) imbalance have been implicated in the pathogenesis of schizophrenia. Using in vivo two-photon microscopy, we examined the dynamic plasticity of dendritic spines of pyramidal neurons (PNs) and "en passant" axonal bouton of parvalbumin-expressing interneurons (PVI...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/s41380-020-01005-w

    authors: Huang Y,Jiang H,Zheng Q,Fok AHK,Li X,Lau CG,Lai CSW

    更新日期:2021-01-20 00:00:00

  • Time-delimited signaling of MET receptor tyrosine kinase regulates cortical circuit development and critical period plasticity.

    abstract::Normal development of cortical circuits, including experience-dependent cortical maturation and plasticity, requires precise temporal regulation of gene expression and molecular signaling. Such regulation, and the concomitant impact on plasticity and critical periods, is hypothesized to be disrupted in neurodevelopmen...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/s41380-019-0635-6

    authors: Chen K,Ma X,Nehme A,Wei J,Cui Y,Cui Y,Yao D,Wu J,Anderson T,Ferguson D,Levitt P,Qiu S

    更新日期:2020-01-03 00:00:00

  • Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes.

    abstract::Although disrupted in schizophrenia 1 (DISC1) has been implicated in many psychiatric disorders, including schizophrenia, bipolar disorder, schizoaffective disorder and major depression, its biological role in these disorders is unclear. To better understand this gene and its role in psychiatric disease, we conducted ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2011.37

    authors: Carless MA,Glahn DC,Johnson MP,Curran JE,Bozaoglu K,Dyer TD,Winkler AM,Cole SA,Almasy L,MacCluer JW,Duggirala R,Moses EK,Göring HH,Blangero J

    更新日期:2011-11-01 00:00:00

  • Candidate genes, pathways and mechanisms for bipolar (manic-depressive) and related disorders: an expanded convergent functional genomics approach.

    abstract::Identifying genes for bipolar mood disorders through classic genetics has proven difficult. Here, we present a comprehensive convergent approach that translationally integrates brain gene expression data from a relevant pharmacogenomic mouse model (involving treatments with a stimulant--methamphetamine, and a mood sta...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/sj.mp.4001547

    authors: Ogden CA,Rich ME,Schork NJ,Paulus MP,Geyer MA,Lohr JB,Kuczenski R,Niculescu AB

    更新日期:2004-11-01 00:00:00

  • Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia.

    abstract::Schizophrenia is a highly heritable disorder with a polygenic pattern of inheritance and a population prevalence of ~1%. Previous studies have implicated synaptic dysfunction in schizophrenia. We tested the accumulated association of genetic variants in expert-curated synaptic gene groups with schizophrenia in 4673 ca...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2011.117

    authors: Lips ES,Cornelisse LN,Toonen RF,Min JL,Hultman CM,International Schizophrenia Consortium.,Holmans PA,O'Donovan MC,Purcell SM,Smit AB,Verhage M,Sullivan PF,Visscher PM,Posthuma D

    更新日期:2012-10-01 00:00:00

  • Gene expression and association analyses of LIM (PDLIM5) in bipolar disorder and schizophrenia.

    abstract::We previously reported that expression level of LIM (ENH, PDLIM5) was significantly and commonly increased in the brains of patients with bipolar disorder, schizophrenia, and major depression. Expression of LIM was decreased in the lymphoblastoid cells derived from patients with bipolar disorders and schizophrenia. LI...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/sj.mp.4001719

    authors: Kato T,Iwayama Y,Kakiuchi C,Iwamoto K,Yamada K,Minabe Y,Nakamura K,Mori N,Fujii K,Nanko S,Yoshikawa T

    更新日期:2005-11-01 00:00:00

  • Connectome imaging for mapping human brain pathways.

    abstract::With the fast advance of connectome imaging techniques, we have the opportunity of mapping the human brain pathways in vivo at unprecedented resolution. In this article we review the current developments of diffusion magnetic resonance imaging (MRI) for the reconstruction of anatomical pathways in connectome studies. ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2017.92

    authors: Shi Y,Toga AW

    更新日期:2017-09-01 00:00:00

  • Disruption of MBD5 contributes to a spectrum of psychopathology and neurodevelopmental abnormalities.

    abstract::Microdeletions of chromosomal region 2q23.1 that disrupt MBD5 (methyl-CpG-binding domain protein 5) contribute to a spectrum of neurodevelopmental phenotypes; however, the impact of this locus on human psychopathology has not been fully explored. To characterize the structural variation landscape of MBD5 disruptions a...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,多中心研究

    doi:10.1038/mp.2013.42

    authors: Hodge JC,Mitchell E,Pillalamarri V,Toler TL,Bartel F,Kearney HM,Zou YS,Tan WH,Hanscom C,Kirmani S,Hanson RR,Skinner SA,Rogers RC,Everman DB,Boyd E,Tapp C,Mullegama SV,Keelean-Fuller D,Powell CM,Elsea SH,Morton CC

    更新日期:2014-03-01 00:00:00

  • An epigenetic mechanism links socioeconomic status to changes in depression-related brain function in high-risk adolescents.

    abstract::Identifying biological mechanisms through which the experience of adversity emerges as individual risk for mental illness is an important step toward developing strategies for personalized treatment and, ultimately, prevention. Preclinical studies have identified epigenetic modification of gene expression as one such ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2016.82

    authors: Swartz JR,Hariri AR,Williamson DE

    更新日期:2017-02-01 00:00:00

  • The dysbindin-containing complex (BLOC-1) in brain: developmental regulation, interaction with SNARE proteins and role in neurite outgrowth.

    abstract::Previous studies have implicated DTNBP1 as a schizophrenia susceptibility gene and its encoded protein, dysbindin, as a potential regulator of synaptic vesicle physiology. In this study, we found that endogenous levels of the dysbindin protein in the mouse brain are developmentally regulated, with higher levels observ...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2009.58

    authors: Ghiani CA,Starcevic M,Rodriguez-Fernandez IA,Nazarian R,Cheli VT,Chan LN,Malvar JS,de Vellis J,Sabatti C,Dell'Angelica EC

    更新日期:2010-02-01 00:00:00

  • Tph2 gene variants modulate response control processes in adult ADHD patients and healthy individuals.

    abstract::Although therapeutic interventions in attention-deficit/hyperactivity disorder (ADHD) still focus on the dopaminergic system, recent studies indicate a serotonergic dysfunction in this disease as well. In that respect, several variants of the tryptophan hydroxylase gene (TPH2), which codes for the rate-limiting enzyme...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2008.39

    authors: Baehne CG,Ehlis AC,Plichta MM,Conzelmann A,Pauli P,Jacob C,Gutknecht L,Lesch KP,Fallgatter AJ

    更新日期:2009-11-01 00:00:00

  • Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma.

    abstract::Psychiatric diseases have a strong heritable component known to not be restricted to DNA sequence-based genetic inheritance alone but to also involve epigenetic factors in germ cells. Initial evidence suggested that sperm RNA is causally linked to the transmission of symptoms induced by traumatic experiences. Here, we...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/s41380-018-0271-6

    authors: Gapp K,van Steenwyk G,Germain PL,Matsushima W,Rudolph KLM,Manuella F,Roszkowski M,Vernaz G,Ghosh T,Pelczar P,Mansuy IM,Miska EA

    更新日期:2020-09-01 00:00:00

  • Identification of a polymorphism in the promoter region of DRD4 associated with the human novelty seeking personality trait.

    abstract::Polymorphism in the human dopamine D4 receptor gene (DRD4) exon III has been associated in some but not all studies of the human personality trait of Novelty Seeking. We searched for polymorphisms in the 5' region of DRD4 and identified six polymorphisms as follows: -1217G Ins/Del, -809G/A, -616C/G, -603T Ins/Del, -60...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/sj.mp.4000563

    authors: Okuyama Y,Ishiguro H,Nankai M,Shibuya H,Watanabe A,Arinami T

    更新日期:2000-01-01 00:00:00

  • The promise and pitfalls of intranasally administering psychopharmacological agents for the treatment of psychiatric disorders.

    abstract::Accumulating research demonstrates the potential of intranasal delivery of psychopharmacological agents to treat a range of psychiatric disorders and symptoms. It is believed that intranasal administration offers both direct and indirect pathways to deliver psychopharmacological agents to the central nervous system. T...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,评审

    doi:10.1038/mp.2015.166

    authors: Quintana DS,Guastella AJ,Westlye LT,Andreassen OA

    更新日期:2016-01-01 00:00:00

  • Childhood trauma, life-time self-harm, and suicidal behaviour and ideation are associated with polygenic scores for autism.

    abstract::Autistic individuals experience significantly elevated rates of childhood trauma, self-harm and suicidal behaviour and ideation (SSBI). Is this purely the result of negative environmental experiences, or does this interact with genetic predisposition? In this study we investigated if a genetic predisposition for autis...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/s41380-019-0550-x

    authors: Warrier V,Baron-Cohen S

    更新日期:2019-10-29 00:00:00

  • Sphingomyelin-induced inhibition of the plasma membrane calcium ATPase causes neurodegeneration in type A Niemann-Pick disease.

    abstract::Niemann-Pick disease type A (NPA) is a rare lysosomal storage disorder characterized by severe neurological alterations that leads to death in childhood. Loss-of-function mutations in the acid sphingomyelinase (ASM) gene cause NPA, and result in the accumulation of sphingomyelin (SM) in lysosomes and plasma membrane o...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2016.148

    authors: Pérez-Cañamás A,Benvegnù S,Rueda CB,Rábano A,Satrústegui J,Ledesma MD

    更新日期:2017-05-01 00:00:00

  • Association and linkage studies between bipolar affective disorder and the polymorphic CAG/CTG repeat loci ERDA1, SEF2-1B, MAB21L and KCNN3.

    abstract::Several reports have suggested the presence of anticipation in bipolar affective disorder (BPAD). In addition, independent studies using the RED (repeat expansion detection) have shown association between BPAD and longer CAG/CTG repeats. Therefore loci with large CAG/CTG repeats are plausible candidates in the inherit...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/sj.mp.4000898

    authors: Meira-Lima IV,Zhao J,Sham P,Pereira AC,Krieger JE,Vallada H

    更新日期:2001-09-01 00:00:00

  • The symptom network structure of depressive symptoms in late-life: Results from a European population study.

    abstract::The network theory conceptualizes mental disorders as complex networks of symptoms influencing each other by creating feedback loops, leading to a self-sustained syndromic constellation. Symptoms central to the network have the greatest impact in sustaining the rest of symptoms. This analysis focused on the network st...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/s41380-018-0232-0

    authors: Belvederi Murri M,Amore M,Respino M,Alexopoulos GS

    更新日期:2020-07-01 00:00:00

  • Reduction of synapsin in the hippocampus of patients with bipolar disorder and schizophrenia.

    abstract::Several studies suggest that decreased expression of presynaptic proteins may be characteristic of schizophrenia. We examined one such protein, synapsin, in schizophrenia and bipolar disorder. Samples of hippocampal tissue from controls (n = 13), patients with schizophrenia (n = 16), or bipolar disorder (n = 6), and s...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/sj.mp.4001158

    authors: Vawter MP,Thatcher L,Usen N,Hyde TM,Kleinman JE,Freed WJ

    更新日期:2002-01-01 00:00:00

  • Dietary triglycerides act on mesolimbic structures to regulate the rewarding and motivational aspects of feeding.

    abstract::Circulating triglycerides (TGs) normally increase after a meal but are altered in pathophysiological conditions, such as obesity. Although TG metabolism in the brain remains poorly understood, several brain structures express enzymes that process TG-enriched particles, including mesolimbic structures. For this reason,...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/mp.2014.31

    authors: Cansell C,Castel J,Denis RG,Rouch C,Delbes AS,Martinez S,Mestivier D,Finan B,Maldonado-Aviles JG,Rijnsburger M,Tschöp MH,DiLeone RJ,Eckel RH,la Fleur SE,Magnan C,Hnasko TS,Luquet S

    更新日期:2014-10-01 00:00:00

  • Translational research in bipolar disorder: emerging insights from genetically based models.

    abstract::Bipolar disorder (BPD) is characterized by vulnerability to episodic depression and mania and spontaneous cycling. Because of marked advances in candidate-gene and genome-wide association studies, the list of risk genes for BPD is growing rapidly, creating an unprecedented opportunity to understand the pathophysiology...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,评审

    doi:10.1038/mp.2010.3

    authors: Chen G,Henter ID,Manji HK

    更新日期:2010-09-01 00:00:00

  • Short-term lithium treatment promotes neuronal survival and proliferation in rat striatum infused with quinolinic acid, an excitotoxic model of Huntington's disease.

    abstract::We assessed the ability of lithium to reduce neurodegeneration and to stimulate cell proliferation in a rat model of Huntington's disease in which quinolinic acid (QA) was unilaterally infused into the striatum. LiCl (0.5-3.0 mEq/kg) was injected subcutaneously 24 h before and 1 h after QA infusion. At 7 days after QA...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/sj.mp.4001463

    authors: Senatorov VV,Ren M,Kanai H,Wei H,Chuang DM

    更新日期:2004-04-01 00:00:00

  • Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD.

    abstract::Genetic and pharmacological studies have emphasised the role of serotonin 5-hydroxytryptamine (5-HT) as a possible etiologic factor in the development of attention-deficit hyperactivity disorder (ADHD). Tryptophan hydroxylase (TPH) is a rate-limiting enzyme in the biosynthesis of serotonin from tryptophan. Originally,...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章

    doi:10.1038/sj.mp.4001698

    authors: Sheehan K,Lowe N,Kirley A,Mullins C,Fitzgerald M,Gill M,Hawi Z

    更新日期:2005-10-01 00:00:00

  • Chromosomal abnormalities and mental illness.

    abstract::Linkage studies of mental illness have provided suggestive evidence of susceptibility loci over many broad chromosomal regions. Pinpointing causative gene mutations by conventional linkage strategies alone is problematic. The breakpoints of chromosomal abnormalities occurring in patients with mental illness may be mor...

    journal_title:Molecular psychiatry

    pub_type: 杂志文章,评审

    doi:10.1038/sj.mp.4001232

    authors: MacIntyre DJ,Blackwood DH,Porteous DJ,Pickard BS,Muir WJ

    更新日期:2003-03-01 00:00:00