Central Effects of Anticholinergic Drugs Measured by the Apomorphine Gnawing Test in Mice

Apomorphine in doses ranging from 10 up to 60 mg/kg given subcutaneously to mice induces only weak gnawing behaviour and 10 mg/kg was without effect. The addition of anticholinergic drugs given 15 min. before 10 mg/kg apomorphine potentiated the gnawing behaviour. 9 tertiary and 3 quaternary drugs were tested. Among these some quinuclidinylesters, scopolamine and benztropine were found to be very active compared with atropine. The quaternary compounds showed much weaker activity than the corresponding tertiary analogues. The gnawing activity produced by atropine plus apomorphine was only weakly antagonized by the apomorphine antagonistic drug spiramide; physostigmine showed a better inhibitory effect and combined treatment with spiramide and physostigmine gave a pronounced antagonistic effect. Since the apomorphine gnawing behaviour is most probably related to an interaction with central dopamine receptors, these findings suggest there is a central counter balancing dopaminergic‐cholinergic system.