Behavioral sensitization following subchronic apomorphine treatment--possible neurochemical basis

Subchronic treatment with the dopamine agonist apomorphine produces a sensitization to the stereotypic effects of subsequent apomorphine challenge. The present study investigated the effects of this subchronic treatment on apomorphine induced stereotypic behavior and striatal dopamine synthesis, release, metabolism, and D2 receptor binding. The pretreatment, which enhanced the behavioral response to apomorphine challenge, also elevated basal dopamine synthesis and metabolism, but left the ability of a challenge dose of apomorphine to inhibit dopamine synthesis and metabolism unaltered. Thus, ongoing dopamine synthesis and extracellular levels of metabolites would be higher following apomorphine challenge in animals treated subchronically with the agonist. In contrast, neither synaptosomal dopamine release in response to depolarizing stimuli nor the density of D2 dopamine receptors was altered by the treatment. Overall, the results suggest that, while we did not find evidence of autoreceptor desensitization per se, apomorphine treatment may result in enhanced extracellular dopamine levels following dopamine agonist challenge to provide a greater stimulation of an intact dopamine receptor system.