Nicotine administration reduces striatal MPP+ levels in mice

Abstract

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.