Article abstract
Nature Neuroscience 12, 1036 - 1041 (2009)
Published online: 13 July 2009 | doi:10.1038/nn.2367
Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations in the NAc
Manuel Mameli1, Briac Halbout2, Cyril Creton1, David Engblom3, Jan Rodriguez Parkitna3, Rainer Spanagel2 & Christian Lüscher1,4,5
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.
- Department of Basic Neurosciences, Medical Faculty, University of Geneva, Geneva, Switzerland.
- Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany.
- Division of Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg, Germany.
- Clinic of Neurology, Department of Clinical Neurosciences, Geneva University Hospital, Geneva, Switzerland.
- Geneva Neuroscience Center, Geneva, Switzerland.
Correspondence to: Christian Lüscher1,4,5 e-mail: christian.luscher@unige.ch
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