Incentive Learning Underlying Cocaine-Seeking Requires mGluR5 Receptors Located on Dopamine D1 Receptor-Expressing Neurons

• DOI: 10.1523/jneurosci.2550-10.2010
• Publication Date: 2010-09-08T16:47:56Z
• Authors: Martin Novak; Briac Halbout; Eoin C. O'Connor; Jan Rodriguez Par...; Tian Su; Minqiang Chai; Hans S. Crombag; Ainhoa Bilbao; Rainer Spanagel; David N. Stephens; Günther Schütz; David Engblom
• Keywords: Associative learning; Stimulus (psychology); Incentive salience

Understanding the psychobiological basis of relapse remains a challenge in developing therapies for drug addiction. Relapse cocaine addiction often occurs following exposure to environmental stimuli previously associated with taking. The metabotropic glutamate receptor, mGluR5, is potentially important this respect; it plays central role several forms striatal synaptic plasticity proposed underpin associative learning and memory processes that enable drug-paired acquire incentive motivational properties trigger relapse. Using cell type-specific RNA interference, we have generated novel mouse line selective knock-down mGluR5 dopamine D1 receptor-expressing neurons. Although mutant mice self-administer cocaine, show reinstatement cocaine-seeking induced by cocaine-paired stimulus impaired. By examining different aspects mice, identify deficits specific reward-paired directly reinforce behavior become attractive, thus eliciting approach toward it. Our findings signaling through located on neurons necessary contribute cue-induced which may