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

Novak, Martin, Halbout, Briac, O'Connor, Eoin, Parkitna, Jan Rodriguez, Su, Tian, Chai, Minqiang, Crombag, Hans S, Bilbao, Ainhoa, Spanagel, Rainer, Stephens, David N, Schütz, Günther and Engblom, David (2010) Incentive Learning Underlying Cocaine-Seeking Requires mGluR5 Receptors Located on Dopamine D1 Receptor-Expressing Neurons. Journal of Neuroscience, 30 (36). pp. 11973-11982. ISSN 02706474

[img]
Preview
PDF - Published Version
Download (1MB) | Preview

Abstract

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

Item Type: Article
Schools and Departments: School of Psychology > Psychology
Depositing User: Eoin O'Connor
Date Deposited: 06 Feb 2012 15:45
Last Modified: 07 Mar 2017 07:32
URI: http://sro.sussex.ac.uk/id/eprint/14272

View download statistics for this item

📧 Request an update