Intra-accumbens protein kinase C inhibitor NPC 15437 blocks amphetamine-produced conditioned place preference in rats

Abstract

In a previous study, intracerebroventricular calcium-dependent protein kinase (PKC) inhibition attenuated cocaine place conditioning. This suggested the hypothesis that intra-nucleus accumbens (NAc) injections of the PKC inhibitor NPC 15437 may block place conditioning produced by NAc injections of amphetamine. An unbiased conditioned place preference paradigm was employed to evaluate the present hypothesis. Thus, during pre-conditioning rats had access to an apparatus consisting of two chambers connected by a tunnel for three 15-min sessions. During 8 conditioning days with the tunnel blocked, one chamber was paired with NAc injections of drug for four 30-min sessions alternating with pairing of the other chamber with NAc injections of saline. Time spent on the drug-paired side was assessed in a final drug-free test session and compared to the amount of time spent there in pre-conditioning; a significant increase was defined as a place preference. Intra-NAc amphetamine (20.0 microg/0.5 microl/side) produced a place preference. This effect was blocked dose dependently by NPC 15437 (0.1, 0.5 and 1.0 microg/0.5 microl/side). NPC 15437 (1.0 microg) alone did not produce a place preference or aversion. None of the doses of NPC 15437 affected the locomotor stimulant effect of intra-NAc amphetamine during conditioning revealing a dissociation between the locomotor stimulating and rewarding effects of intra-NAc amphetamine. Results implicate PKC in the NAc in reward-related learning. More work is needed to elucidate the signaling pathways involved in this type of learning.