Neuron
Volume 59, Issue 3, 14 August 2008, Pages 497-508
Journal home page for Neuron

Article
Glutamate Receptors on Dopamine Neurons Control the Persistence of Cocaine Seeking

https://doi.org/10.1016/j.neuron.2008.07.010Get rights and content
Under an Elsevier user license
open archive

Summary

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.

SYSNEURO
HUMDISEASE
PROTEINS

Cited by (0)

7

These authors contributed equally to this work

8

These authors contributed equally to this work

9

Present address: Department of Clinical and Experimental Medicine, Linköping University, 58185 Linköping, Sweden

10

Present address: Laboratorio de Psicofarmacología del etanol., Universitat Jaume I. SN, 12071 Castelló, Spain