CHRONIC ORAL NICOTINE ADMINISTRATION AFFECTS THE CIRCADIAN-RHYTHM OF DOPAMINE AND 5-HYDROXYTRYPTAMINE METABOLISM IN THE STRIATA OF MICE

The effect of chronic oral administration of nicotine on the circadian rhythm of striatal dopamine (DA) and 5-hydroxytryptamine (5-HT) was s tudied in mice. Mice receiving nicotine in their drinking water and co ntrol mice drinking tap water were killed at 05:00, 11:00, 15:00 or 21 :00 hours on the 50th day of chronic administration. The plasma concen trations of nicotine and cotinine, as well the striatal concentrations of DA, 5-HT and their metabolites 3,4 dihydroxyphenylacetic acid (DOP AC), 3-methoxytyramine (3-MT) homovanilic acid (HVA) and 5-hydroxyindo leacetic acid (5-HIAA) were estimated. The largest plasma concentratio ns of nicotine and cotinine were found at 05:00, when they were more t han double the concentrations found at the other times studied. This i ndicates that the mice, typically for nocturnal animals, consumed most of their daily drinking water at night. In the control mice, the stri atal DA and 3-MT concentrations showed circadian variation and were lo west at 11:00. The 5-HIAA concentrations also varied, being highest at 11:00. In the nicotine-treated mice the circadian variations in stria tal monoamines were altered and more pronounced than in the controls. The concentrations of DA, DOPAC, HVA and 5-HIAA were highest at 11:00 and that of 5-HT at 21:00. The striatal DA, DOPAC, HVA and 5-HIAA conc entrations in the nicotine-treated mice were significantly higher at 1 1:00 and the 5-HT concentrations at 21:00 than in the control mice, an d, in contrast to the control mice, in the mice treated with chronic n icotine no circadian rhythm was observed in the 3-MT. No elevation of striatal DA metabolites occurred in the nicotine-treated mice compared with the controls when the plasma nicotine concentration was at its p eak at 05:00. This finding suggests development of tolerance to the ni cotine-induced changes in striatal DA metabolism Further, our findings suggest that the chronic administration of nicotine in the drinking w ater of mice alters the circadian pattern of striatal DA and, to a les ser extent, that of 5-HT, and thus may affect the functions regulated by these transmitters.