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11. D1 Dopamine Receptor-Mediated LTP at GABA Synapses Encodes Motivation to Self-Administer Cocaine in Rats.

Author

Krawczyk, Michal, Mason, Xenos, DeBacker, Julian, Sharma, Robyn, Normandeau, Catherine P., Hawken, Emily R., Di Prospero, Cynthia, Chiang, Cindy, Martinez, Audrey, Jones, Andrea A., Doudnikoff, Évelyne, Caille, Stephanie, Bézard, Erwan, Georges, François, and Dumont, Éric C.

Subjects
MOTIVATION (Psychology), DRUG addiction, DOPAMINE receptors, GABA, LABORATORY rats
Abstract

Enhanced motivation to take drugs is a central characteristic of addiction, yet the neural underpinning of this maladaptive behavior is still largely unknown. Here, we report a Dl-like dopamine receptor (DRDl)-mediated long-term potentiation of GABAA-IPSCs (D1-LTPGABA) in the oval bed nucleus of the stria terminalis that was positively correlated with motivation to self-administer cocaine in rats. Likewise, in vivo intra-oval bed nucleus of the stria terminalis DRD1 pharmacological blockade reduced lever pressing for cocaine more effectively in rats showing enhanced motivation toward cocaine. D1-LTPGABA resulted from enhanced function and expression of G-protein-independent DRD1 coupled to c-Src tyrosine kinases and required local release of neurotensin. There was no D1-LTPGABA in rats that self-administered sucrose, in those with limited cocaine self-administration experience, or in those that received cocaine passively (yoked). Therefore, our study reveals a novel neurophysiological mechanism contributing to individual motivation to self-administer cocaine, a critical psychobiological element of compulsive drug use and addiction. [ABSTRACT FROM AUTHOR]

Published
2013
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