Both glutamate and nitric oxide have been found to be critical for the formation of learned behaviors. Pretreatment of rats systemically with MK-801 (a glutamate antagonist) or N-nitro-L-arginine methyl ester (L- NAME), a nitric oxide synthase inhibitor, prevented the acquisition of cocaine-induced conditioned increases in locomotor activity. Neither compound, however, was able to attenuate the expression of cocaine conditioned behaviors once established. These findings indicate that while glutamate and nitric oxide play a role in the formation of cocaine conditioned increases in locomotor activity, they are not involved in mediating its expression. Pretreatment of rats with eticlopride prior to a series of extinction sessions prevented the expression of cocaine conditioned behaviors but had no effect on the extinction process. It seems that intact DA D2 function is necessary for extinction to occur. Neither the D1 antagonist SCH 23390 nor apomorphine had an appreciable effect on the extinction process.
