RESPONSE-REINFORCEMENT LEARNING IS DEPENDENT ON N-METHYL-N-ASPARTATE RECEPTOR ACTIVATION IN THE NUCLEUS-ACCUMBENS CORE

The nucleus accumbens, a site within the ventral striatum. is best kno wn for its prominent role in mediating the reinforcing effects of drag s of abuse such as cocaine, alcohol, and nicotine. Indeed, it is gener ally believed that this structure subserves motivated behaviors, such as feeding, drinking, sexual behavior, and exploratory locomotion, whi ch are elicited by natural rewards or incentive stimuli. A basic rule of positive reinforcement is that motor responses will increase in mag nitude and vigor if followed by a rewarding event, It is likely, there fore, that the nucleus accumbens may serve as a substrate for reinforc ement learning, However, there is surprisingly little information conc erning the neural mechanisms by which appetitive responses are learned , In the present study, we report that treatment of the nucleus accumb ens core with the selective competitive N-methyl-D-aspartate (NMDA) an tagonist 2-amino-5-phosphonopentanoic acid (AP-5; 5 nmol/0.5 mu l bila terally) impairs response-reinforcement learning in the acquisition of a simple lever-press task to obtain food, Once the rats learned the t ask, AP-5 had no effect, demonstrating the requirement of NMDA recepto r-dependent plasticity in the early stages of learning. Infusion of AP -5 into the accumbens shell produced a much smaller impairment of lear ning, Additional experiments showed that AP-5 core-treated rats had no rmal feeding and locomotor responses and were capable of acquiring sti mulus-reward associations. We hypothesize that stimulation of NMDA rec eptors within the accumbens core is a key process through which motor responses become established in response to reinforcing stimuli, Furth er, this mechanism, may also play a critical role in the motivational and addictive properties of drugs of abuse.