Contrasting effects on methamphetamine sensitization of ceruletide, a cholecystokinin-like decapeptide, and haloperidol.

Ceruletide, a cholecystokinin-like decapeptide, and haloperidol show neuroleptic actions through inhibition of dopamine release and blockade of dopamine receptors, respectively. In this study, the effects of both drugs on methamphetamine sensitization were assessed by means of ambulation in mice. The enhancement in ambulation increase caused by five repeated administrations of methamphetamine (2 mg/kg, SC) at 3- to 4-day intervals was dose-dependently reduced when it was administered simultaneously with ceruletide (0.01-0.1 mg/kg, SC) or haloperidol (0.03-0.3 mg/kg, SC). However, only haloperidol could inhibit the induction of methamphetamine sensitization as assessed by challenge with methamphetamine alone. Post-treatment with ceruletide (0.03 mg/kg) 3 h after each methamphetamine accelerated, whereas such post-treatment with ceruletide (0.1 mg/kg) or haloperidol (0.03-0.3 mg/kg) delayed, the induction of methamphetamine sensitization. On the other hand, mice given five pretreatments with ceruletide (0.01-0.1 mg/kg) or haloperidol (0.03-0.3 mg/kg) at 3- to 4-day intervals did not exhibit any significant change in the sensitivity to methamphetamine. The present results suggest that, in contrast to the dose-dependent inhibition of methamphetamine sensitization in the simultaneous administration and post-treatment schedules, although both drugs can antagonize the acute stimulant effect of methamphetamine.