Inhibition of methamphetamine sensitization by post-methamphetamine treatment with SCH 23390 or haloperidol.

Methamphetamine (2 mg/kg SC) increased ambulation in mice for about 3 h, with a peak effect at around 40 min after the administration, and its repeated administration induced sensitization. Both SCH 23390 (0.03 mg/kg SC) and haloperidol (0.4 mg/kg SC), dopamine D1 and D2 receptor antagonists, respectively, completely inhibited not only the acute stimulant effect of methamphetamine but also its sensitization when repeated methamphetamine was repeatedly combined with either of these drugs. Moreover, treatment with SCH 23390 2-5 h or haloperidol 1-5 h after each methamphetamine administration significantly antagonized methamphetamine sensitization. The maximal inhibitory effect was observed in the schedules of 3-h post-methamphetamine treatment for both drugs. However, treatments with SCH 23390 or haloperidol at 0.5 h, 6 h and 24 h after methamphetamine had no such inhibitory effect. The mice treated with SCH 23390 or haloperidol after each saline administration (the control administration for methamphetamine) did not show significant change in the sensitivity to methamphetamine. These results suggest that methamphetamine has an effect on both dopamine D1 and D2 receptors for several hours even after cessation of its acute stimulant effect, and that such an effect is involved in the induction of sensitization to the stimulant effect of methamphetamine on ambulation in mice.