NMDA, but not dopamine D2, receptors in the rat nucleus accumbens are involved in guidance of instrumental behavior by stimuli predicting reward magnitude

Expectancy of future reward is an important factor guiding the speed of instrumental behavior. The present study sought to explore whether signals transmitted via the NMDA subtype of glutamate receptors and via dopamine D-2 receptors in the nucleus accumbens (NAc) are critical for the determination of reaction times (RTs) of instrumental responses by the expectancy of future reward. A simple RT task for rats demanding conditioned lever release was used in which the upcoming reward magnitude (5 or 1 pellet) was signaled in advance by discriminative stimuli. In trained rats, RTs of conditioned responses with expectancy of a high reward magnitude were found to be significantly shorter. The shortening of RTs by stimuli predictive of high reward to be obtained was dose-dependently impaired by bilateral intra-NAc infusion of the competitive NMDA antagonist DL-2-amino-5-phosphonovaleric acid (APV) (1, 2, or 10 mg in 0.5 ml/side), but not by infusion of the preferential dopamine D-2 antagonist haloperidol (5 and 12.5 mu g in 0.5 mu l/side) or by infusion of vehicle (0.5 ml/side). In conclusion, the data reveal that in well trained animals stimulation of intra-NAc NMDA, but not of dopamine D-2, receptors, is critically involved in guiding the speed of instrumental responses according to stimuli predictive of the upcoming reward magnitude.