Augmentation of sensitivity to ambulation-increasing effect of apomorphine induced by repeated administration in mice

Effect of apomorphine on ambulatory activity in mice was investigated after single and repeated administration. The activity was measured by a tilting-type round activity cage of 20 cm in diameter. Single administration of apomorphine at doses of 0.016-0.13 mg/kg sc tended to decrease the ambulatory activity, while doses of 0.5-4 mg/kg sc increased it. Repeated administration of apomorphine (0.5 mg/kg sc) at intervals of 1 hr, 1 day and 7 days induced an augmentation of sensitivity to the ambulation-increasing effect of the drug regardless of the administration intervals. The same treatments of apomorphine (1 mg/kg sc) produced neither augmentation nor tolerance to it. However, the mice exhibited stereotyped behaviors such as sniffing and climbing after the repeated administration, although they hardly exhibited the stereotyped behaviors on the 1st administration. The augmentation of sensitivity, once produced, was well maintained 1 month after cessation of the repeated administration. The augmentation of sensitivity to apomorphine was produced in mice which had repeatedly exposed to both experimental situations in which the ambulation was freely allowed and perfectly restricted, respectivity, during presence of the acute drug effect.