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

Details

Serval ID
serval:BIB_E0D34C58E5CA
Type
Article: article from journal or magazin.
Collection
Publications
Title
Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations in the NAc.
Journal
Nature neuroscience
Author(s)
Mameli M., Halbout B., Creton C., Engblom D., Parkitna J.R., Spanagel R., Lüscher C.
ISSN
1546-1726 (Electronic)
ISSN-L
1097-6256
Publication state
Published
Issued date
08/2009
Peer-reviewed
Oui
Volume
12
Number
8
Pages
1036-1041
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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
Animals, Cocaine/pharmacology, Cocaine-Related Disorders/physiopathology, Dopamine Uptake Inhibitors/pharmacology, Glutamic Acid/metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net/drug effects, Nerve Net/metabolism, Neural Pathways/drug effects, Neural Pathways/metabolism, Neuronal Plasticity/drug effects, Neuronal Plasticity/physiology, Nucleus Accumbens/drug effects, Nucleus Accumbens/metabolism, Organ Culture Techniques, Receptors, Metabotropic Glutamate/drug effects, Receptors, Metabotropic Glutamate/metabolism, Recurrence, Substance Withdrawal Syndrome/genetics, Substance Withdrawal Syndrome/metabolism, Substance Withdrawal Syndrome/physiopathology, Synaptic Transmission/drug effects, Synaptic Transmission/physiology, Ventral Tegmental Area/drug effects, Ventral Tegmental Area/metabolism
Pubmed
Web of science
Create date
31/01/2017 15:40
Last modification date
20/08/2019 16:05
Usage data