Early post-treatment 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 effect 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 sensitization were haloperidol-dose-dependently inhibited. Moreover, treatment with haloperidol (0.1 and 0.4 mg/kg) 3 h following each methamphetamine administration, which per se did not affect the acute ambulation increase caused by methamphetamine, could protect against the induction of methamphetamine sensitization in a dose-dependent manner, whereas treatment with haloperidol after 24 h did not show such protective action. The present results suggest that blockade of the dopamine receptors at an early period following each administration of methamphetamine may be responsible for the delay in development of methamphetamine sensitization as expressed by ambulatory activity of mice.