Behavioral and biochemical effects of nicotine in an MPTP-induced mouse model of Parkinson's disease.
This study examined the effects of nicotine on locomotor activity and on the level of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum and olfactory tubercle of mice that had been treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP significantly lowered the spontaneous locomotor activity 1-2 weeks and 2 months after 2 injections of MPTP (30 mg/kg SC, 24 hr apart) in young adult (3 months) and old mice (22-24 months old). The effect of nicotine on locomotion was biphasic; an initial stimulation of locomotor (0-5 min after nicotine) followed by a depressant period lasting from 5 to 20 min after injection. Tolerance to the depressant effect of nicotine developed after the 5th day of daily injections of nicotine (0.4 mg/kg SC, twice daily). Tolerance did not occur by day 8 to the initial stimulatory effect of nicotine. A similar effect of nicotine on locomotor activity was seen in mice treated with MPTP. The levels of DOPAC and HVA in the striatum were reduced by about 20% in the chronic nicotine-treated animals. The levels of DOPAC, DA, and HVA were reduced in the MPTP-treated mice; however, acute and chronic nicotine did not cause an additional change in the amine levels. The results suggest that nicotine has an influence on locomotor activity in MPTP-treated mice and that this effect is not due to changes in DA receptor activity in the striatum caused by chronic nicotine.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis; D004361:Drug Tolerance; D005260:Female; D006719:Homovanillic Acid / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D009830:Olfactory Bulb / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy*; D011725:Pyridines / Q000494:pharmacology*
D011725:Pyridines; D015102:3,4-Dihydroxyphenylacetic Acid; D009538:Nicotine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid