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 developmen t of sensitization was inhibited when MAP was administered in combinat ion with HPD in the repeated administration schedule. However, any dos e of HPD could not ameliorate the established MAP sensitization. Where as, the mice experienced the repeated treatment with HPD 0.4mg/kg show ed an increase in the MAP sensitivity. The present results suggest tha t HPD, at comparatively higher doses, produces a denervation supersens itivity of postsynaptic dopamine receptors, and shows protective actio n on the development of MAP sensitization. However, it is also suggest ed that the established MAP sensitization is irreversible even after t he treatment with HPD.