Glutamate receptors on dopamine neurons control the persistence of cocaine seeking.

Détails

ID Serval
serval:BIB_B146F3D10F6F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Glutamate receptors on dopamine neurons control the persistence of cocaine seeking.
Périodique
Neuron
Auteur(s)
Engblom D., Bilbao A., Sanchis-Segura C., Dahan L., Perreau-Lenz S., Balland B., Parkitna J.R., Luján R., Halbout B., Mameli M., Parlato R., Sprengel R., Lüscher C., Schütz G., Spanagel R.
ISSN
1097-4199 (Electronic)
ISSN-L
0896-6273
Statut éditorial
Publié
Date de publication
14/08/2008
Peer-reviewed
Oui
Volume
59
Numéro
3
Pages
497-508
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Cocaine strengthens excitatory synapses onto midbrain dopamine neurons through the synaptic delivery of GluR1-containing AMPA receptors. This cocaine-evoked plasticity depends on NMDA receptor activation, but its behavioral significance in the context of addiction remains elusive. Here, we generated mice lacking the GluR1, GluR2, or NR1 receptor subunits selectively in dopamine neurons. We report that in midbrain slices of cocaine-treated mice, synaptic transmission was no longer strengthened when GluR1 or NR1 was abolished, while in the respective mice the drug still induced normal conditioned place preference and locomotor sensitization. In contrast, extinction of drug-seeking behavior was absent in mice lacking GluR1, while in the NR1 mutant mice reinstatement was abolished. In conclusion, cocaine-evoked synaptic plasticity does not mediate concurrent short-term behavioral effects of the drug but may initiate adaptive changes eventually leading to the persistence of drug-seeking behavior.

Mots-clé
Animals, Behavior, Animal, Cocaine-Related Disorders/metabolism, Cocaine-Related Disorders/physiopathology, Conditioning, Operant/drug effects, Conditioning, Operant/physiology, Dopamine/metabolism, Excitatory Amino Acid Antagonists/pharmacology, In Vitro Techniques, Membrane Potentials/drug effects, Membrane Potentials/genetics, Mice, Mice, Knockout, Motor Activity/physiology, Neuronal Plasticity/drug effects, Neuronal Plasticity/genetics, Neurons/drug effects, Neurons/physiology, Patch-Clamp Techniques, Receptors, AMPA/deficiency, Receptors, Glutamate/physiology, Receptors, N-Methyl-D-Aspartate/deficiency, Time Factors, Valine/analogs & derivatives, Valine/pharmacology, Ventral Tegmental Area/cytology, gamma-Aminobutyric Acid/pharmacology
Pubmed
Web of science
Open Access
Oui
Création de la notice
31/01/2017 16:42
Dernière modification de la notice
08/05/2019 23:52
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