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Publication : Absence of NMDA receptors in dopamine neurons attenuates dopamine release but not conditioned approach during Pavlovian conditioning.

First Author  Parker JG Year  2010
Journal  Proc Natl Acad Sci U S A Volume  107
Issue  30 Pages  13491-6
PubMed ID  20616081 Mgi Jnum  J:162402
Mgi Id  MGI:4818834 Doi  10.1073/pnas.1007827107
Citation  Parker JG, et al. (2010) Absence of NMDA receptors in dopamine neurons attenuates dopamine release but not conditioned approach during Pavlovian conditioning. Proc Natl Acad Sci U S A 107(30):13491-6
abstractText  During Pavlovian conditioning, phasic dopamine (DA) responses emerge to reward-predictive stimuli as the subject learns to anticipate reward delivery. This observation has led to the hypothesis that phasic dopamine signaling is important for learning. To assess the ability of mice to develop anticipatory behavior and to characterize the contribution of dopamine, we used a food-reinforced Pavlovian conditioning paradigm. As mice learned the cue-reward association, they increased their head entries to the food receptacle in a pattern that was consistent with conditioned anticipatory behavior. D1-receptor knockout (D1R-KO) mice had impaired acquisition, and systemic administration of a D1R antagonist blocked both the acquisition and expression of conditioned approach in wild-type mice. To assess the specific contribution of phasic dopamine transmission, we tested mice lacking NMDA-type glutamate receptors (NMDARs) exclusively in dopamine neurons (NR1-KO mice). Surprisingly, NR1-KO mice learned at the same rate as their littermate controls. To evaluate the contribution of NMDARs to phasic dopamine release in this paradigm, we performed fast-scan cyclic voltammetry in the nucleus accumbens of awake mice. Despite having significantly attenuated phasic dopamine release following reward delivery, KO mice developed cue-evoked dopamine release at the same rate as controls. We conclude that NMDARs in dopamine neurons enhance but are not critical for phasic dopamine release to behaviorally relevant stimuli; furthermore, their contribution to phasic dopamine signaling is not necessary for the development of cue-evoked dopamine or anticipatory activity in a D1R-dependent Pavlovian conditioning paradigm.
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