Effects of haloperidol on the methamphetamine sensitization: assessment by ambulatory activity in mice.

Haloperidol (HPD: 0.0063, 0.025, 0.1 and 0.4 mg/kg, s.c.) reduced dose-dependently the ambulation-increasing effect of methamphetamine (MAP: 2 mg/kg, s.c.) in mice. The repeated administration of MAP elicited a sensitization to its ambulation-increasing effect, and the development of sensitization was inhibited when MAP was administered in combination with HPD in the repeated administration schedule. However, any dose of HPD could not ameliorate the established MAP sensitization. Whereas, the mice experienced the repeated treatment with HPD 0.4 mg/kg showed an increase in the MAP sensitivity. The present results suggest that HPD, at comparatively higher doses, produces a denervation supersensitivity of postsynaptic dopamine receptors, and shows protective action on the development of MAP sensitization. However, it is also suggested that the established MAP sensitization is irreversible even after the treatment with HPD.