Further studies of the mechanism behind scopolamine-induced reversal of antistereotypic and cataleptogenic effects of neuroleptics in rats.

Scopolamine is known to attenuate the amphetamine antagonistic and cataleptogenic effect of selective DA D-2 antagonists. To study further the influence of other receptor systems three approaches were taken: concomitant treatment with receptor blockers (scopolamine, prazosin and ketanserin) and a selective D-2 antagonist YM 09151-2, testing of a neuroleptic droperidol, with mixed D-2, alpha 1 and 5-HT2 antagonistic properties and testing a selective D-1 antagonist SCH 23390. Scopolamine markedly attenuated both effects of YM 09151-2 and droperidol. In contrast neither prazosin nor ketanserin influenced the effects of YM 09151-2. Furthermore, prazosin did not influence the interaction between scopolamine and YM 09151-2 in the tests of stereotypy and catalepsy. Scopolamine did not change the amphetamine antagonistic potency of SCH 23390, but decreased moderately its cataleptogenic potency. It is concluded that 5-HT2 and alpha 1-adrenergic receptor blockade are of minor importance in order to determine the sensitivity of a DA D-2 antagonist to the reversal induced by scopolamine. Thus, our earlier hypothesis, that DA D-1 receptor blockade is the main mechanism stabilizing these neuroleptic effects against scopolamine reversal, are further supported by the present experiments.