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Tani Y, Saito K, Tsuneyoshi A, Imoto M, Ohno T: Nicotinic acetylcholine receptor (nACh-R) agonist-induced changes in brain monoamine turnover in mice. Psychopharmacology. 1997 Feb;129(3):225-32.
The aim of the present study was to evaluate the effects of nicotinic acetylcholine receptor (nACh-R) agonists such as (-)-nicotine and related compounds on brain monoamine turnover. A single administration of (-)-nicotine (0.04, 0.2, 1.0, and 5.0 mg/kg SC) increased both noradrenaline (NA) and dopamine (DA) turnover in a dose-dependent manner, and the maximum effects were achieved 30 min after treatment with (-)-nicotine (1.0 mg/kg). The effect of (-)-nicotine on serotonin (5-HT) turnover was complicated; 5-HT turnover was increased at a low dose of (-)-nicotine (0.04 mg/kg) but decreased at a high dose (1.0 mg/kg). The (-)-nicotine (1.0 mg/kg)-induced changes in monoamine turnover were blocked by pretreatment with the centrally acting nACh-R channel blocker mecamylamine (2.0 mg/kg i.p.) but not by hexamethonium (2.0 mg/kg i.p.). These findings indicate that systemically administered (-)-nicotine can enhance brain NA and DA turnover and affect 5-HT turnover, both of which are mediated by central nACh-R. The changes in the monoamine turnover induced by (+/-)-anabasine were similar to those induced by (-)-nicotine, while (-)-lobeline and (-)-cytisine had little effect, and 1,1-dimethyl-4-phenyl-piperazinium (DMPP) increased NA and 5-HT turnover but not DA turnover at all doses tested. (S)-3-Methyl-5-(l-methyl-2- pyrrolidinyl) isoxazole (ABT-418), a selective neuronal nACh-R agonist, increased NA, DA and 5-HT turnover, but had a weaker effect on DA turnover than NA and 5-HT turnover. In addition, 9-amino-1,2,3,4-tetrahydroacridine (THA), an acetylcholine esterase inhibitor, also increased monoamine turnover in the brain. Pretreatment with mecamylamine completely blocked the THA-induced increase in NA and 5-HT turnover, but not in DA turnover, suggesting that the nACh-R system is involved in the THA-induced increase in brain NA and 5-HT turnover. On the other hand, (-)-cytisine, a partial agonist for the beta 2 subunit containing nACh-R, completely inhibited the nACh-R agonist- and THA-induced increases in NA turnover, but not in DA turnover, and normalized the changes in 5-HT turnover. In conclusion, the subtypes of nACh-Rs mediating DA turnover may be different from those mediating NA and 5-HT turnover in the CNS. |
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