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Reward and motor learning in mice lacking D2 receptors in dopaminergic neurons

Thursday, October 11, 2012 — Poster Session IV

2:00 p.m. – 4:00 p.m.

Natcher Conference Center, Building 45




  • K.B. Holroyd
  • R.L. Fuino
  • R. Bock
  • A.R. Kaplan
  • E.P. Bello
  • M. Rubinstein
  • V.A. Alvarez


D2 dopamine receptors are thought to modulate the reinforcing properties of cocaine and to regulate motor learning. However, identifying the role of these receptors is complicated by the existence of both postsynaptic D2 receptors and presynaptic autoreceptors, which inhibit dopamine release. The goal of this study is to determine the specific role of D2 autoreceptors in drug-seeking behavior and motor learning. Littermate wild type and D2 autoreceptor knockout mice (autoD2 KO) were trained for 15 days on a cued-operant task in which one nose poke earned an intravenous infusion of cocaine. We found that autoD2 KO mice acquired self-administration behavior similarly to wild type mice and showed similar extinction behavior when no cue light was present. In the presence of the cue light, however, autoD2 KO mice were more resistant to extinction. Similarly, autoD2 mice showed a trend towards increased sensitivity to the cue light during reinstatement. A cocaine dose response indicated that autoD2 KO mice have higher responding for low doses of cocaine. In addition, autoD2 KO mice out-performed wild type when using a double-speed rotarod but showed similar performance on a normal speed rotorod.

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