Effects of chronic oral nicotine treatment and its withdrawal on locomotoractivity and brain monoamines in mice

The effects of chronic nicotine and its withdrawal on locomotor activity an d brain monoamines were studied using a new animal model of administering n icotine in the drinking water to male NMRI mice as the sole source of fluid . Locomotor activity as well as cerebral concentrations of dopamine (DA), 3 ,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytr yptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NA) an d 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG) were measured post mortem on the 50th day of nicotine administration or at 12-14 or 23-25 h after wi thdrawal. On the 50th day of drug administration the chronically nicotine-t reated mice were more active than the control mice drinking tap water and a fter withdrawal from nicotine the locomotor activity dropped to the level o f the controls. In chronically nicotine-treated mice the striatal concentra tions of DOPAC, HVA and 5-HIAA, hypothalamic 5-HIAA and NA as well as corti cal NA were elevated. The concentrations of DOPAC, HVA and 5-HIAA reversed to control levels within 23-25 h after withdrawal from nicotine. The nicoti ne-induced elevation of the hypothalamic NA concentration was still signifi cant at 23-25 h after withdrawal. At 12-14 h after withdrawal the hypothala mic concentration of MOPEG was increased. In conclusion, our findings on lo comotor activity suggest that administration of nicotine in the drinking wa ter to mice for several weeks seems to be a relevant method to study nicoti ne dependence. Furthermore, the alterations found in cerebral DA, NA and 5- HT metabolism during chronic nicotine administration indicate that all thre e cerebral transmitter monoamines might be involved in nicotine dependence and withdrawal. (C) 2000 Elsevier Science B.V. All rights reserved.