Chronic nicotine administration in the drinking water affects the striataldopamine in mice

Although tobacco contains a large variety of substances, its addictive prop erties are most probably due to the reinforcing actions of nicotine that mo tivates continued tobacco use. Animals and humans self-administer nicotine, a response that appears to invoke the mesolimbic dopamine system and to be common to other abused drugs. The present article reviews animal models to administer nicotine chronically. We also describe a new animal model in wh ich nicotine is given to mice in drinking water as their sole source of flu id. This treatment produced nicotine plasma concentrations comparable to or above those found in smokers. We found that mice withdrawn from nicotine w ere tolerant to the effects of nicotine challenge on striatal dopamine meta bolism as well as on body temperature and locomotor activity. Furthermore, H-3-nicotine binding in the cortex and midbrain was significantly increased in mice withdrawn from nicotine. The last part of the article will focus o n the effects of this chronic nicotine treatment on striatal dopamine. Dopa mine and its metabolites and locomotor activity were increased in the foren oon in mice still drinking nicotine solutions. We also report recent data i n which chronic nicotine administration in the drinking water enhanced the effect of dopamine receptor agonist, quinpirole, on striatal metabolism. Th e animal model described appears to be a relevant method for studying the m echanisms that are thought to be involved in nicotine dependence. (C) 2000 Elsevier Science Inc.