Referenced in: none

Automatically associated channels: Kv2.1

Title: Role of NMDA receptors in dopamine neurons for plasticity and addictive behaviors.

Authors: Larry S Zweifel, Emanuela Argilli, Antonello Bonci, Richard D Palmiter

Journal, date & volume: Neuron, 2008 Aug 14 , 59, 486-96

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18701073

Abstract
A single exposure to drugs of abuse produces an NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) of AMPA receptor (AMPAR) currents in DA neurons; however, the importance of LTP for various aspects of drug addiction is unclear. To test the role of NMDAR-dependent plasticity in addictive behavior, we genetically inactivated functional NMDAR signaling exclusively in DA neurons (KO mice). Inactivation of NMDARs results in increased AMPAR-mediated transmission that is indistinguishable from the increases associated with a single cocaine exposure, yet locomotor responses to multiple drugs of abuse were unaltered in the KO mice. The initial phase of locomotor sensitization to cocaine is intact; however, the delayed sensitization that occurs with prolonged cocaine withdrawal did not occur. Conditioned behavioral responses for cocaine-testing environment were also absent in the KO mice. These findings provide evidence for a role of NMDAR signaling in DA neurons for specific behavioral modifications associated with drug seeking behaviors.