Nicotine administration reduces striatal MPP plus levels in mice

Nicotine administration has previously been shown to attenuate nigrostriata l damage in animal models of Parkinson's disease, including the 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse. The present experim ents 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.) 1 0 min prior to MPTP (30 mg/kg s.c.) followed by three subsequent doses of n icotine at 15-min intervals according to a dose schedule previously shown t o be neuroprotective. The mice were sacrificed 1.5, 4 and 8 h after MPTP ad ministration 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. Exper iments done to examine the effect of age showed that the decrease was obser ved 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-i nduced model of nigrostriatal degeneration. In summary, these results sugge st that nicotine may exert its neuroprotective action against nigrostriatal degeneration, at least in part, by decreasing striatal MPP+ levels. (C) 20 01 Elsevier Science B.V. All rights reserved.