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Behav Brain Res. 2019 May 2;363:77-82. doi: 10.1016/j.bbr.2019.01.037. Epub 2019 Jan 31.

Ablation of NMDA receptors in dopamine neurons disrupts attribution of incentive salience to reward-paired stimuli.

Author information

1
Department of Molecular Neuropharmacology, Institute of Pharmacology of the Polish Academy of Sciences, Smętna 12, 31-343, Krakow, Poland.
2
Department of Molecular Neuropharmacology, Institute of Pharmacology of the Polish Academy of Sciences, Smętna 12, 31-343, Krakow, Poland. Electronic address: Jan.Rodriguez@if-pan.krakow.pl.

Abstract

Midbrain dopamine (DA) neurons play a crucial role in the formation of conditioned associations between environmental cues and appetitive events. Activation of N-methyl-d-aspartate (NMDA) receptors is a key mechanism responsible for the generation of conditioned responses of DA neurons to reward cues. Here, we tested the effects of the cell type-specific inactivation of NMDA receptors in DA neurons in adult mice on stimulus-reward learning. Animals were trained in a Pavlovian learning paradigm in which they had to learn the predictive value of two conditioned stimuli, one of which (CS+) was paired with the delivery of a water reward. Over the course of conditioning, mutant mice learned that the CS+ predicted reward availability, and they approached the reward receptacle more frequently during CS+ trials than CS- trials. However, conditioned responses to the CS+ were weaker in the mutant mice, possibly indicating that they did not attribute incentive salience to the CS+. To further assess whether the attribution of incentive salience was impaired by the mutation, animals were tested in a conditioned reinforcement test. The test revealed that mutant mice made fewer instrumental responses paired with CS+ presentation, confirming that the CS+ had a weaker incentive value. Taken together, these results indicate that reward prediction learning does occur in the absence of NMDA receptors in DA neurons, but the ability of reward-paired cues to invigorate and reinforce behavior is attenuated.

KEYWORDS:

Associative learning; Conditioned reinforcement; Dopamine; Incentive salience; NMDA receptor

PMID:
30711444
DOI:
10.1016/j.bbr.2019.01.037

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