Effects of nicotine on 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine-induced depression of striatal dopamine content and spontaneous locomotor activity in C57 black mice

The present study examined the effects of nicotine on the levels of dopamine and its metabolite 3,4-dihydroxy-phenylacetic acid (DOPAC) in the striatum and on spontaneous locomotor activity of C57 black mice that had been treated with the neurotoxin l-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). The levels of dopamine and DOPAC in the striatum were significantly reduced 10 days after two injections of MPTP (40 mg kg(-1), i.p., 24 h apart) in mice. Chronic treatment of nicotine (2.0 mg kg(-1), s.c., four injections per day) did not influence the striatal content of dopamine and DOPAC, but it significantly antagonised MPTP-induced depression of dopamine. However, the chronic nicotine treatment did not significantly affect MPTP-induced depression of DOPAC. It was demonstrated that the lethal effect of MPTP was also partly protected by the chronic nicotine treatment. The chronic nicotine treatment also significantly protected MPTP-depressed spontaneous locomotor activity in mice. The results suggest that both MPTP-depressed behaviour and MPTP-induced striatal dopamine depletion in C57 black mice are partly protected by chronic nicotine treatment. (C) 1998 The Italian Pharmacological Society.