Effect of haloperidol on the behavioral stimulation by N-cyanomethylmethamphetamine, a main product of smoking methamphetamine mixed with tobacco

Abstract

N-Cyanomethylmethamphetamine is a main product of smoking methamphetamine mixed with tobacco. The aim of this experiment was to evaluate the effects of haloperidol on behavioral stimulation by N-cyanomethylmethamphetamine (3 mg/kg s.c.) in terms of ambulation in mice. Repeated administration of N-cyanomethylmethamphetamine, carried out 5 × at 3-day intervals, induced a sensitization to its ambulation-increasing effect. Haloperidol (0.01, 0.03, 0.1 and 0.3 mg/kg s.c.) significantly inhibited not only the acute stimulant effect of N-cyanomethylmethamphetamine but also the induction of sensitization. The dose-effect curves for the inhibitory effects of haloperidol on the N-cyanomethylmethamphetamine-induced ambulatory stimulation were almost the same between the drug-naive and N-cyanomethylmethamphetamine-sensitized mice. Moreover, such behavioral characteristics of N-cyanomethylmethamphetamine; the behavioral stimulant effect, the induction of sensitization following repeated administration, and the inhibition of its effects by haloperidol, were qualitatively the same as those of methamphetamine (2 mg/kg s.c.). These results suggest that N-cyanomethylmethamphetamine possesses methamphetamine-like central stimulant effect and that D 2 dopaminergic mechanisms are involved in the effect of N-cyanomethylmethamphetamine.