CONTRASTING EFFECTS ON METHAMPHETAMINE SENSITIZATION OF CERULETIDE, ACHOLECYSTOKININ-LIKE DECAPEPTIDE, AND HALOPERIDOL

Ceruletide, a cholecystokinin-like decapeptide, and haloperidol show n euroleptic actions through inhibition of dopamine release and blockade of dopamine receptors, respectively. In this study, the effects of bo th drugs on methamphetamine sensitization were assessed by means of am bulation in mice. The enhancement in ambulation increase caused by fiv e repeated administrations of methamphetamine (2 mg/kg, SC) at 3- to 4 -day intervals was dose-dependently reduced when it was administered s imultaneously with ceruletide (0.01-0.1 mg/kg, SC) or haloperidol (0.0 3-0.3 mg/kg, SC). However, only haloperidol could inhibit the inductio n of methamphetamine sensitization as assessed by challenge with metha mphetamine alone. Post-treatment with ceruletide (0.03 mg/kg) 3 h afte r each methamphetamine accelerated, whereas such post-treatment with c eruletide (0.1 mg/kg) or haloperidol (0.03-0.3 mg/kg) delayed, the ind uction 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 significan t change in the sensitivity to methamphetamine. The present results su ggest that, in contrast to the dose-dependent inhibition of methamphet amine sensitization by haloperidol, ceruletide may result in only slig ht modification of methamphetamine sensitization in the simultaneous a dministration and post-treatment schedules, although both drugs can an tagonize the acute stimulant effect of methamphetamine.