Dual effects of nicotine on neuroleptic-induced changes of striatal dopamine metabolism in mice.
The effect of nicotine on the neuroleptic-induced changes in striatal dopamine (DA) metabolism of mice was studied. To investigate the mechanism of action of nicotine, its interactions with apomorphine (APO) and gamma-hydroxybutyric acid (GHBA) were also investigated. Mice were given nicotine, (0.3-3 mg/kg subcutaneously) repeatedly (4 times) at 30 min. intervals. Haloperidol (HAL), (+/-)-sulpiride (SUL), APO or GHBA were administered after the second nicotine dose. Hexamethonium was given to prevent the effects of nicotine on autonomic ganglia. The striatal contents of DA and of its metabolites homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) were measured. The drug-induced hypothermia in mice was controlled by increasing ambient temperature. At ambient temperature of 32-34 degrees nicotine and HAL increased the striatal DOPAC and HVA contents additively, whereas APO counteracted the effects of nicotine at this ambient temperature. At 20-22 degrees nicotine decreased the 3-MT content which indicates reduced release of DA. In hypothermic mice nicotine inhibited better the HAL- and SUL-induced increases of HVA content than those of DOPAC content suggesting that the neuroleptic-induced increases in DOPAC and HVA contents are mediated partly by different mechanisms. In APO-treated mice both the GHBA- and nicotine-induced decreases of 3-MT content fell further. GHBA did not alter the nicotine-induced decrease of 3-MT content and so this effect of nicotine may be mediated indirectly via GABAergic neurones. Unlike GHBA and APO nicotine decreased 3-MT content only in hypothermic mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Haikala
H
H
Department of Pharmacy, University of Helsinki, Finland.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D012978:Sodium Oxybate / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology
D014150:Antipsychotic Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D009538:Nicotine; D012978:Sodium Oxybate; D013469:Sulpiride; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine; D006719:Homovanillic Acid