Synaptic Neurotransmission Depression in Ventral Tegmental Dopamine Neurons and Cannabinoid-Associated Addictive Learning

Hdl Handle:
http://hdl.handle.net/10675.2/618
Title:
Synaptic Neurotransmission Depression in Ventral Tegmental Dopamine Neurons and Cannabinoid-Associated Addictive Learning
Authors:
Liu, Zhiqiang; Han, Jing; Jia, Lintao; Maillet, Jean-Christian; Bai, Guang; Xu, Lin; Jia, Zhengping ( 0000-0003-4413-5364 ) ; Zheng, Qiaohua; Zhang, Wandong; Monette, Robert; Merali, Zul; Zhu, Zhou; Wang, Wei; Ren, Wei; Zhang, Xia
Abstract:
Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction.
Editors:
Mei, Lin
Citation:
PLoS One. 2010 Dec 20; 5(12):e15634
Issue Date:
20-Dec-2010
URI:
http://hdl.handle.net/10675.2/618
DOI:
10.1371/journal.pone.0015634
PubMed ID:
21187978
PubMed Central ID:
PMC3004941
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Neurology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorLiu, Zhiqiangen_US
dc.contributor.authorHan, Jingen_US
dc.contributor.authorJia, Lintaoen_US
dc.contributor.authorMaillet, Jean-Christianen_US
dc.contributor.authorBai, Guangen_US
dc.contributor.authorXu, Linen_US
dc.contributor.authorJia, Zhengpingen_US
dc.contributor.authorZheng, Qiaohuaen_US
dc.contributor.authorZhang, Wandongen_US
dc.contributor.authorMonette, Roberten_US
dc.contributor.authorMerali, Zulen_US
dc.contributor.authorZhu, Zhouen_US
dc.contributor.authorWang, Weien_US
dc.contributor.authorRen, Weien_US
dc.contributor.authorZhang, Xiaen_US
dc.contributor.editorMei, Lin-
dc.date.accessioned2012-10-26T16:26:54Z-
dc.date.available2012-10-26T16:26:54Z-
dc.date.issued2010-12-20en_US
dc.identifier.citationPLoS One. 2010 Dec 20; 5(12):e15634en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid21187978en_US
dc.identifier.doi10.1371/journal.pone.0015634en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/618-
dc.description.abstractDrug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction.en_US
dc.rightsLiu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectElectrophysiologyen_US
dc.subjectNeuroscienceen_US
dc.subjectNeurochemistryen_US
dc.subjectNeurochemicalsen_US
dc.subjectDopamineen_US
dc.subjectLearning and Memoryen_US
dc.subjectMedicineen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectElectrophysiologyen_US
dc.subjectMental Healthen_US
dc.subjectPsychiatryen_US
dc.subjectGambling Addictionen_US
dc.subjectPsychologyen_US
dc.subjectCognitive Psychologyen_US
dc.subjectLearningen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBehavior, Addictiveen_US
dc.subject.meshCannabinoidsen_US
dc.subject.meshElectrophysiologyen_US
dc.subject.meshEndocytosisen_US
dc.subject.meshLong-Term Potentiationen_US
dc.subject.meshLong-Term Synaptic Depressionen_US
dc.subject.meshNeuronsen_US
dc.subject.meshRatsen_US
dc.subject.meshReceptor, Cannabinoid, CB1en_US
dc.subject.meshReceptors, AMPAen_US
dc.subject.meshReceptors, N-Methyl-D-Aspartateen_US
dc.subject.meshSynaptic Transmissionen_US
dc.subject.meshVentral Tegmental Areaen_US
dc.titleSynaptic Neurotransmission Depression in Ventral Tegmental Dopamine Neurons and Cannabinoid-Associated Addictive Learningen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3004941en_US
dc.contributor.corporatenameDepartment of Neurology-
dc.contributor.corporatenameCollege of Graduate Studies-
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