Effect of duration of haloperidol treatment on DA receptor supersensitization in aging C57BL/6J mice.

Apomorphine-induced behavior, striatal [3H]spiperone binding, and striatal choline acetyltransferase (ChAT) activity were assessed in 6 1/2, 13, and 27-30 month-old male C57BL/6J mice following 0, 30, 60 or 90 days treatment with the dopaminergic (DA) antagonist haloperidol. Both apomorphine-induced behavior and [3H]spiperone binding (Bmax) increased linearly with duration of haloperidol treatment, with no detectable age difference in the degree of supersensitization, although basal receptor density declined with age. Middle- and old-aged mice showed prolonged stereotypic behavior relative to young mice, suggesting slower apomorphine clearance. No differences in ChAT activity were detected with either age or duration of haloperidol treatment. Although the group means of binding and behavior were highly related, the within group correlations were poor. Overall, the results suggest that aged animals are capable of DA receptor supersensitization when given a sufficient stimulus--in this case, relatively long treatment regimes. Previously reported deficits in neuroleptic-induced supersensitization in old mice may be confined to relatively short treatment periods at low doses.