Alterations in the effects of dopamine agonists and antagonists on general activity in rats following chronic morphine treatment

Results of two experiments revealed that morphine produced both time-and dose-dependent effects on the general activity of rats following a single acute administration, depression being observed 30 min after the injection and hyperactivity at 150 min. Tolerance to the depressive effects of morphine was observed within 7 days of chronic, once daily treatments, the depression being replaced by a hyperactivity that included a high degree of self-directed oral stereotyped behaviour. Dose-response analyses of the effects of d-amphetamine, an indirectly acting dopamine agonist, and apomorphine, a directly acting dopamine agonist, revealed a shift in the dose-response curves following chronic morphine treatment, indicating that the animals were supersensitive to these agents. Conversely, the dose-response curve for pimozide, a directly acting dopamine antagonist, was shifted in a direction indicating that the animals were subsensitive to this agent. The dose-response curve for haloperidol, another dopamine antagonist, was unchanged. These findings are consistent with the hypothesis that an increase in the number of dopamine receptors may develop during chronic treatment with morphine.