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Articles, Behavioral/Systems/Cognitive

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

Martin Novak, Briac Halbout, Eoin C. O'Connor, Jan Rodriguez Parkitna, Tian Su, Minqiang Chai, Hans S. Crombag, Ainhoa Bilbao, Rainer Spanagel, David N. Stephens, Günther Schütz and David Engblom
Journal of Neuroscience 8 September 2010, 30 (36) 11973-11982; https://doi.org/10.1523/JNEUROSCI.2550-10.2010
Martin Novak
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Briac Halbout
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Eoin C. O'Connor
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Jan Rodriguez Parkitna
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Tian Su
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Minqiang Chai
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Hans S. Crombag
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Ainhoa Bilbao
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Rainer Spanagel
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David N. Stephens
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Günther Schütz
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David Engblom
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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.

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The Journal of Neuroscience: 30 (36)
Journal of Neuroscience
Vol. 30, Issue 36
8 Sep 2010
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Incentive Learning Underlying Cocaine-Seeking Requires mGluR5 Receptors Located on Dopamine D1 Receptor-Expressing Neurons
Martin Novak, Briac Halbout, Eoin C. O'Connor, Jan Rodriguez Parkitna, Tian Su, Minqiang Chai, Hans S. Crombag, Ainhoa Bilbao, Rainer Spanagel, David N. Stephens, Günther Schütz, David Engblom
Journal of Neuroscience 8 September 2010, 30 (36) 11973-11982; DOI: 10.1523/JNEUROSCI.2550-10.2010

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Incentive Learning Underlying Cocaine-Seeking Requires mGluR5 Receptors Located on Dopamine D1 Receptor-Expressing Neurons
Martin Novak, Briac Halbout, Eoin C. O'Connor, Jan Rodriguez Parkitna, Tian Su, Minqiang Chai, Hans S. Crombag, Ainhoa Bilbao, Rainer Spanagel, David N. Stephens, Günther Schütz, David Engblom
Journal of Neuroscience 8 September 2010, 30 (36) 11973-11982; DOI: 10.1523/JNEUROSCI.2550-10.2010
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