The effect of apomorphine and clonidine on locomotor activity in mice after long term treatment with haloperidol.

1. Mice were given haloperidol (approximately 3 mg.kg-1 day-1) or vehicle for 21 days and then withdrawn from the drug. All tests were performed 4 days after withdrawal. 2. Haloperidol treated mice (premedicated with reserpine plus alpha-methyl-p-tyrosine) displayed an increased locomotor response to apomorphine and to apomorphine plus clonidine, but neither haloperidol- or vehicle-treated animals revealed any stimulant response to clonidine. 3. In mice which had not been pretreated with reserpine plus alpha-methyl-p-tyrosine, clonidine produced a significant stimulation of locomotor activity in animals withdrawn from haloperidol but not in those withdrawn from the vehicle. Phenoxybenzamine blocked the locomotor stimulat difference between these two groups, but did not completely antagonized the stimulant effect of clonidine in mice withdrawn from haloperidol. Pimozide was largely effective in blocking the clonidine-induced stimulation. Co-administration of phenoxybenzamine and pimozide was completely effective in blocking the stimulant effect of clonidine in mice withdrawn from haloperidol. 4. The evidence for a change in catecholamine receptor sensitivity was supported compared to the vehicle-treated animals. 5. The data suggest that there is a change in the functional responsiveness of both adrenergic and dopaminergic receptors after withdrawal from long term haloperidol treatment.