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Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area

Published in Science. 2013, vol. 341, no. 6153, p. 1521-5
Abstract Drug-evoked synaptic plasticity in the mesolimbic system reshapes circuit function and drives drug-adaptive behavior. Much research has focused on excitatory transmission in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). How drug-evoked synaptic plasticity of inhibitory transmission affects circuit adaptations remains unknown. We found that medium spiny neurons expressing dopamine (DA) receptor type 1 (D1R-MSNs) of the NAc project to the VTA, strongly preferring the GABA neurons of the VTA. Repeated in vivo exposure to cocaine evoked synaptic potentiation at this synapse, occluding homosynaptic inhibitory long-term potentiation. The activity of the VTA GABA neurons was thus reduced and DA neurons were disinhibited. Cocaine-evoked potentiation of GABA release from D1R-MSNs affected drug-adaptive behavior, which identifies these neurons as a promising target for novel addiction treatments.
Keywords AnimalsCocaine/pharmacologyCocaine-Related Disorders/physiopathologyDopaminergic Neurons/metabolismMiceMice, Inbred C57BLMice, TransgenicNeuronal Plasticity/drug effectsSynaptic Transmission/drug effects/physiologyVentral Tegmental Area/metabolismGamma-Aminobutyric Acid/drug effects/metabolism
PMID: 24072923
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Research group Mécanismes cellulaires de la dépendance et de l'addiction (520)
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BOCKLISCH, Christina et al. Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area. In: Science, 2013, vol. 341, n° 6153, p. 1521-5. doi: 10.1126/science.1237059 https://archive-ouverte.unige.ch/unige:33842

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Deposited on : 2014-01-29

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