INHIBITION BY MK-801 OF COCAINE-INDUCED SENSITIZATION, CONDITIONED PLACE PREFERENCE, AND DOPAMINE-RECEPTOR SUPERSENSITIVITY IN MICE

Repeated administration of cocaine led to increases in ambulation-acce lerating activity (sensitization) and conditioned place preference (CP P). Dopamine (DA)-receptor supersensitivity was also developed in coca ine-induced sensitized and CPP mice. An N-methyl-D-aspartate (NMDA)-re ceptor antagonist, MK-801, blocked simultaneously developments of coca ine-induced behavioral sensitization, CPP, and DA-receptor supersensit ivity. Furthermore, MK-801 inhibited a apomorphine-induced striatal do paminergic action: climbing behavior. These results suggest that the c ocaine-induced dopaminergic behaviors such as sensitization to ambulat ory activity and CPP may be produced via activation of the NMDA recept or. The development of postsynaptic DA-receptor supersensitivity may b e an underlying common mechanism that mediates cocaine-induced behavio ral sensitization and CPP.