抄録
In this study, effects of nicotine on locomotor sensitization to methamphetamine in mice were investigated to assess whether nicotine modified induction and expression of psychotoxic action of methamphetamine. Although nicotine (0.03-1 mg/kg s.c.) had no effect at first administration, 5-time nicotine administrations at 3-day intervals progressively developed a significant locomotor stimulant effect, and caused an enhanced sensitivity (cross-sensitization) to methamphetamine (2 mg/kg s.c.). Five-time administrations of methamphetamine (2 mg/kg) at 3-day intervals produced not only a locomotor sensitization to methamphetamine itself, but also a cross-sensitization to nicotine (0.1-1 mg/kg). Nicotine (0.03-1 mg/kg) did not affect the locomotor stimulant effect of methamphetamine (2 mg/kg) in the drug-naive mice. However, nicotine acted dose-dependently to reduce the progressive enhancement of the locomotor stimulant effect of methamphetamine during 5-time Repeated administrations. Mice treated with coadministration of methamphetamine with nicotine (1 mg/kg) showed less sensitization to metharnphetamine than mice treated with methamphetamine alone. In addition, nicotine (1 mg/kg) inhibited the locomotor stimulant effect of methamphetamine in mice sensitized to methamphetamine. These results suggest that methamphetamine and nicotine produce a symmetrical cross-sensitization, although nicotine may act to inhibit the induction and expression of locomotor sensitization to methamphetamine in mice.
