Comparison of the effects of prototypical behavioral stimulants on locomotor activity and rotational behavior in rats

The present study was performed to characterize on rotational behavior the dose- and time-effect relationship of four prototypical behavioral stimulants that interact with dopamine systems via different mechanisms of action. Drug effects on rotational behavior was compared with effects on locomotor activity. The drugs examined were apomorphine (0.03-1.0 mg/kg), d-amphetamine (0.1-3.0 mg/kg), cocaine (3.0-56 mg/kg), and caffeine (10-100 mg/kg). SKF-38393 (0.3-10 mg/kg), a dopamine receptor agonist that has only modest effects on locomotor activity, was tested as a comparison. In rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the nigrostriatal tract, d-amphetamine and cocaine dose dependently increased both the duration and the maximum number of turns/10 min, whereas apomorphine and caffeine increased only the duration of turning. There was a significant correlation of the effects of the four drugs on rotational behavior with effects on locomotor activity, but effects across drugs were not identical. Dose-response curves revealed potency differences among drugs in their effects on the two behaviors (e.g., apomorphine stimulated rotational behavior at a lower dose than it stimulated locomotor activity, whereas the converse was true with caffeine). Different mechanisms of action of these drugs might account for the differences in their effects on these behaviors.