Chronic nicotine administration in the drinking water affects the striatal dopamine in mice.
Although tobacco contains a large variety of substances, its addictive properties are most probably due to the reinforcing actions of nicotine that motivates continued tobacco use. Animals and humans self-administer nicotine, a response that appears to involve 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 which nicotine is given to mice in drinking water as their sole source of fluid. This treatment produced nicotine plasma concentrations comparable to or above those found in smokers. We found that mice withdrawn from nicotine were tolerant to the effects of nicotine challenge on striatal dopamine metabolism as well as on body temperature and locomotor activity. Furthermore, 3H-nicotine binding in the cortex and midbrain was significantly increased in mice withdrawn from nicotine. The last part of the article will focus on the effects of this chronic nicotine treatment on striatal dopamine. Dopamine and its metabolites and locomotor activity were increased in the forenoon in mice still drinking nicotine solutions. We also report recent data in which chronic nicotine administration in the drinking water enhanced the effect of dopamine receptor agonist, quinpirole, on striatal metabolism. The animal model described appears to be a relevant method for studying the mechanisms that are thought to be involved in nicotine dependence.
Pietilä
K
K
Division of Pharmacology and Toxicology, Department of Pharmacy, P.O. Box 56, FIN-00014 University of Helsinki, Helsinki, Finland. kirsi.pietila@helsinki.fi
Ahtee
L
L
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004326:Drinking; D004361:Drug Tolerance; D051379:Mice; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D019257:Quinpirole / Q000494:pharmacology; D014029:Tobacco Use Disorder / Q000209:etiology
D019257:Quinpirole; D009538:Nicotine; D004298:Dopamine