RT Journal Article
SR Electronic
T1 Incentive Learning Underlying Cocaine-Seeking Requires mGluR5 Receptors Located on Dopamine D1 Receptor-Expressing Neurons
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 11973
OP 11982
DO 10.1523/JNEUROSCI.2550-10.2010
VO 30
IS 36
A1 Novak, Martin
A1 Halbout, Briac
A1 O'Connor, Eoin C.
A1 Rodriguez Parkitna, Jan
A1 Su, Tian
A1 Chai, Minqiang
A1 Crombag, Hans S.
A1 Bilbao, Ainhoa
A1 Spanagel, Rainer
A1 Stephens, David N.
A1 Schütz, Günther
A1 Engblom, David
YR 2010
UL http://www.jneurosci.org/content/30/36/11973.abstract
AB 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.