Dissociable effects of antagonism of NMDA and AMPA/KA receptors in the nucleus accumbens core and shell on cocaine-seeking behavior

The purpose of the present experiment was to investigate the involvement of NMDA and AMPA/KA receptors in the nucleus accumbens core and shell in the control over cocaine-seeking behavior by drug-associated cues. Rats were tr ained under a second-order schedule of reinforcement for cocaine with five infusions of cocaine being available in each daily session. The NMDA recept or antagonist AP-5 and the AMPA/KA receptor antagonist LY293558 were infuse d directly into the core or shell. LY293558 infused into the core produced a dose-dependent decrease in responding during both the first, cocaine-unaf fected interval and also after cocaine had been self-administered in subseq uent intervals. By contrast, AP-5 infused into the core had no effect on re sponding. Infusion of AP-5 into the shell had the limited effect of decreas ing responding during the second interval only. There were no effects of LY 293558 infused into the shell. These results indicate that NMDA and AMPA re ceptor-mediated glutamate transmission in the core and shell are dissociabl y involved in cocaine-seeking behavior controlled in part by drug-associate d cues. (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.