Repeated amphetamine and fencamfamine: sensitization and reciprocal cross-sensitization

The repeated administration of amphetamine and related dopamine agonists results in an augmented or sensitized behavioral response to subsequent administration of these drugs. In addition to reflecting central nervous system plasticity, this altered response profile may also represent an animal model for stimulant-induced psychosis in humans. Therefore, considerable interest has been focused on determining the mechanisms underlying the sensitization process. One approach involves comparing and contrasting the effects of various stimulants possessing different molecular mechanisms of action. In this regard, some evidence suggests that fencamfamine and amphetamine interact with pharmacologically distinguishable dopamine pools. Therefore, we compared the behavioral response profiles to the repeated administration of behaviorally comparable doses of amphetamine and fencamfamine, and examined the pattern of cross-interaction between the two stimulants. Fencamfamine produced an amphetamine-like pattern of behavioral augmentation, and both drugs exhibited identical patterns of cross-sensitization. These results lend further support to the sensitization model of stimulant psychosis. Possible dopaminergic mechanisms underlying the sensitization are discussed.