Conditioned saccharin avoidance and sensitization to drugs of abuse

Abstract

Saccharin avoidance conditioned by drugs of abuse (CSA) has been interpreted as an expression of the appetitive, dopamine-dependent, properties of the drug. Repeated exposure to these drugs induces an increase (sensitization) of their motor stimulant properties associated with differential changes in DA transmission in the NAc shell and core. The present study investigated the changes in drug CSA induced by schedules of repeated drug exposure that induce behavioral sensitization. CSA was performed in a two-bottle choice paradigm with two saccharin-drug associations in rats previously sensitized to morphine, cocaine, amphetamine and nicotine. In control rats morphine (1 and 5mg/kg s.c.), cocaine (5 and 10mg/kg i.p.), amphetamine (0.25 and 0.5mg/kg s.c.) and nicotine (0.4 mg/kg s.c.) induced dose-dependent CSA. Sensitization to morphine, cocaine and nicotine, which is known to reduce the responsiveness of NAc shell DA to the same drugs, also reduced CSA. In contrast, sensitization to amphetamine, that does not affect the responsiveness of NAc shell DA to the drug, failed to affect CSA. The results are consistent with the hypothesis that NAc shell DA is a substrate of the appetitive properties of drugs of abuse.