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Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations in the NAc

Halbout, Briac
Engblom, David
Parkitna, Jan Rodriguez
Spanagel, Rainer
Published in Nature Neuroscience. 2009, vol. 12, no. 8, p. 1036-41
Abstract Addictive drugs hijack mechanisms of learning and memory that normally underlie reinforcement of natural rewards and induce synaptic plasticity of glutamatergic transmission in the mesolimbic dopamine (DA) system. In the ventral tegmental area (VTA), a single exposure to cocaine efficiently triggers NMDA receptor-dependent synaptic plasticity in DA neurons, whereas plasticity in the nucleus accumbens (NAc) occurs only after repeated injections. Whether these two forms of plasticity are independent or hierarchically organized remains unknown. We combined ex vivo electrophysiology in acute brain slices with behavioral assays modeling drug relapse in mice and found that the duration of the cocaine-evoked synaptic plasticity in the VTA is gated by mGluR1. Overriding mGluR1 in vivo made the potentiation in the VTA persistent. This led to synaptic plasticity in the NAc, which contributes to cocaine-seeking behavior after protracted withdrawal. Impaired mGluR1 function in vulnerable individuals could represent a first step in the recruitment of the neuronal network that underlies drug addiction.
Keywords AnimalsCocaine/pharmacologyCocaine-Related Disorders/physiopathologyDopamine Uptake Inhibitors/pharmacologyGlutamic Acid/metabolismMiceMice, Inbred C57BLMice, TransgenicNerve Net/drug effects/metabolismNeural Pathways/drug effects/metabolismNeuronal Plasticity/drug effects/physiologyNucleus Accumbens/drug effects/metabolismOrgan Culture TechniquesReceptors, Metabotropic Glutamate/drug effects/metabolismRecurrenceSubstance Withdrawal Syndrome/genetics/metabolism/physiopathologySynaptic Transmission/drug effects/physiologyVentral Tegmental Area/drug effects/metabolism
PMID: 19597494
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Research group Mécanismes cellulaires de la dépendance et de l'addiction (520)
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MAMELI, Manuel et al. Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations in the NAc. In: Nature Neuroscience, 2009, vol. 12, n° 8, p. 1036-41. doi: 10.1038/nn.2367 https://archive-ouverte.unige.ch/unige:3824

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Deposited on : 2009-10-14

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