Dopamine antagonist effects on behavior maintained by cocaine and alfentanil in rhesus monkeys

The effects of dopamine (DA) antagonists that act on either the D1 site (SCH 39166), the D2 site (eticlopride), or both sites non-selectively (cis-flupenthixol) were evaluated for their effects on behavior maintained by cocaine or alfentanil in rhesus monkeys. Each of these drugs suppressed rates of responding maintained by cocaine or alfentanil. Larger doses of each of the DA antagonists were necessary to suppress cocaine- as opposed to alfentanil-maintained responding, suggesting that cocaine but not alfentanil was able to antagonize the rate-suppressing effects of the antagonists. There was little evidence, under these conditions of acute administration, that the DA antagonists modified the reinforcing effects of either cocaine or alfentanil. This would have been observed by an antagonist-induced increase in the ED(50) of the reinforcing drugs and, although such an increase was seen occasionally with cocaine, it was never statistically significant. The effects of rate-suppressing doses of each of the antagonists on directly observable behavior indicated a rapid onset and relatively short duration of action of intravenously administered SCH 39166 and eticlopride. cis-Flupenthixol had a much slower onset of action. Each of the DA antagonists produced similar increases in measures of sedation and relaxation. These data suggest very similar behavioral effects of DA antagonists that act selectively on D1 or D2 receptors or act non-selectively on both DA receptors.