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Title

Glutamate receptors on dopamine neurons control the persistence of cocaine seeking

Authors
Engblom, David
Bilbao, Ainhoa
Sanchis-Segura, Carles
Perreau-Lenz, Stephanie
Parkitna, J. R.
Lujan, Rafael
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Published in Neuron. 2008, vol. 59, no. 3, p. 497-508
Abstract 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.
Keywords AnimalsBehavior, AnimalCocaine-Related Disorders/metabolism/ physiopathologyConditioning, Operant/drug effects/physiologyDopamine/ metabolismExcitatory Amino Acid Antagonists/pharmacologyMembrane Potentials/drug effects/geneticsMiceMice, KnockoutMotor Activity/physiologyNeuronal Plasticity/drug effects/geneticsNeurons/drug effects/ physiologyPatch-Clamp TechniquesReceptors, AMPA/deficiencyReceptors, Glutamate/ physiologyReceptors, N-Methyl-D-Aspartate/deficiencyTime FactorsValine/analogs & derivatives/pharmacologyVentral Tegmental Area/cytologyGamma-Aminobutyric Acid/pharmacology
Stable URL http://archive-ouverte.unige.ch/unige:10243
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Identifiers
PMID: 18701074
Structures
Research group Mécanismes cellulaires de la dépendance et de l'addiction (520)
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