Repeated low dose apomorphine induced subsensitivity of presynaptic dopamine receptors

The influence of repeated administration of a low dose of apomorphine on presynaptic dopamine (DA) receptors was examined. (1) Male ddY mice were given a low dose of apomorphine (0.2 mg/kg) for 7 days. Following 2 drug-free days they were given apomorphine (0.2 mg/kg, IP), after which cage climbing behavior and the level of 3-methoxytyramine (3MT) in striatum was measured. Mice became tolerant to apomorphine's activity-depressing effect and 3MT-decreasing effect. (2) Mice were given haloperidol (1 mg/kg) for 7 days. Then after 2 drug-free days they were given 0.2 or 1.0 mg/kg of apomorphine, after which cage climbing behavior was measured. One mg/kg of apomorphine significantly increased cage climbing behavior, indicating that supersensitivity of postsynaptic DA receptors was induced by haloperidol, but the activity-depressing effect of 0.2 mg/kg of apomorphine was not modified. The results suggest that subsensitivity of presynaptic DA receptors participates in the tolerance to the activity-depressing effect of a low dose of apomorphine.