EARLY POSTTREATMENT WITH HALOPERIDOL RETARDS INDUCTION OF METHAMPHETAMINE SENSITIZATION IN MICE

The repeated administration of methamphetamine (2 mg/kg s.c.) at 3- to 4-day intervals induced sensitization to its ambulation-increasing ef fect in mice. When the simultaneous administration of methamphetamine with haloperidol (0.025, 0.1 and 0.4 mg/kg s.c.) was carried out, the acute ambulation-increasing effect as well as the development of sensi tization were haloperidol-dose-dependently inhibited. Moreover, treatm ent with haloperidol (0.1 and 0.4 mg/kg) 3 h following each methamphet amine administration, which per se did not affect the acute ambulation increase caused by methamphetamine, could protect against the inducti on of methamphetamine sensitization in a dose-dependent manner, wherea s treatment with haloperidol after 24 h did not show such protective a ction. The present results suggest that blockade of the dopamine recep tors at an early period following each administration of methamphetami ne may be responsible for the delay in development of methamphetamine sensitization as expressed by ambulatory activity of mice.