Effects of the competitive N-methyl-D-aspartate receptor antagonist, CPP, on the development and expression of conditioned hyperactivity and sensitization induced by cocaine.

This study used novel behavioral measures to examine the effects of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist, CPP, on the development and expression of conditioned hyperactivity and sensitization produced with cocaine. The first experiment confirmed that horizontal locomotor activity measured in the central zone of an activity enclosure could be increased by 10.0 mg/kg cocaine. This increased activity showed sensitization after repeated cocaine injections, and it could be conditioned to the test environment. Subsequent experiments demonstrated that CPP (0.2 and 0.4 nmol, i.c.v.) could block the development, but not the expression, of conditioned hyperactivity and sensitization in the central zone. These findings confirm that NMDA receptors are critically involved in the development of conditioned hyperactivity and sensitization, but indicate that such receptors may not be necessary for the expression of these neurobehavioral adaptations.