Nicotine administration reduces striatal MPP+ levels in mice.

Nicotine administration has previously been shown to attenuate nigrostriatal damage in animal models of Parkinson's disease, including the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse. The present experiments were done to determine whether nicotine may be exerting its effects by altering striatal levels of 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of MPTP. Mice were injected with nicotine (0.33-1 mg/kg i.p.) 10 min prior to MPTP (30 mg/kg s.c.) followed by three subsequent doses of nicotine at 15-min intervals according to a dose schedule previously shown to be neuroprotective. The mice were sacrificed 1.5, 4 and 8 h after MPTP administration and striatal MPP+ levels measured. Nicotine administration (0.33-1.0 mg/kg) resulted in a time-dependent decline in striatal MPP+ levels that was significantly enhanced over that in saline injected animals. Experiments done to examine the effect of age showed that the decrease was observed in older (8-10 months) but not young (6-8 weeks) mice, a finding which may explain some of the variability in the effect of nicotine in the MPTP-induced model of nigrostriatal degeneration. In summary, these results suggest that nicotine may exert its neuroprotective action against nigrostriatal degeneration, at least in part, by decreasing striatal MPP+ levels.