PHARMACOLOGICAL SPECIFICITY OF N-METHYL-D-ASPARTATE DISCRIMINATION INRATS

The purpose of this study was to provide further information on the us efulness of N-methyl-D-aspartate (NMDA) discrimination in rats as a be havioral model for NMDA receptor activation. The pharmacological speci ficity of the NMDA discriminative stimulus was examined in rats traine d to discriminate 30 mg/kg, i.p. NMDA from saline using a 2-lever fixe d-ratio (FR) 32 food reinforcement schedule. Pharmacologically diverse centrally-acting agents were examined for their ability to substitute for NMDA. Morphine did not substitute for NMDA; neither did the centr al stimulants, caffeine and (+)-amphetamine, which produced a maximum mean of only 16 and 35% NMDA-lever responding, respectively. Pentylene tetrazol and picrotoxin also did not substitute for NMDA. Compounds in teracting with cholinergic neurotransmission including nicotine, physo stigmine, arecoline and mecamylamine, produced at best, only intermedi ate levels of NMDA-lever responding (32-61 %), with the highest levels of NMDA-lever responding generally occurring at doses that also reduc ed rates of responding. These results suggest that the discriminative stimulus properties of NMDA are dissimilar from those of a number of c entrally-acting drugs. Combined with the results of studies indicating that the NMDA discriminative stimulus can be antagonized by competiti ve NMDA antagonists, these results provide further evidence that NMDA receptor activation is the basis of NMDA discrimination and that this model may be useful for studying site-selective NMDA agonists and anta gonists.