Enhanced motor activity and brain dopamine turnover in mice during long-term nicotine administration in the drinking water

Nicotine was administered chronically to NMRI mice in their drinking water in gradually increasing concentrations to measure gross motor activity and brain nicotine concentrations over 24 h on the 50th day of nicotine administration. Also, the striatal postmortem tissue concentrations and accumbal extracellular concentrations of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured to study the role of dopaminergic systems in nicotine-induced hyperactivity in mice. The cerebral nicotine concentration was at its highest at the end of the dark period. The activity of nicotine-treated mice and their striatal DA metabolism were parallelly increased at 2 to 3 h after midnight and in the forenoon. Microdialysis experiments carried out in the forenoon showed that the extracellular levels of DA and DOPAC were elevated in the nucleus accumbens of these mice. Nicotine did not alter the circadian rhythmicity of activity in the mice. Rather, our findings suggest that the mice consume more nicotine when active and this might lead to enhanced release and metabolism of DA and further, to enhanced motor behavior. These findings support the suggestions that nicotine's effects on limbic and striatal DA are critical for its stimulating effects. (C) 2001 Elsevier Science Inc. All rights reserved.