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Nicotinic acetylcholine receptor (nACh-R) agonist-induced changes in brain monoamine turnover in mice

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Abstract

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 (1.0mg/kg)-induced changes in monoamine turnover were blocked by pretreatment with the centrally acting nACh-R channel blocker mecamylamine (2.0 mg/kg IP) but not by hexamethonium (2.0 mg/kg IP). 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 l,l-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-l,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 β2 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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  1. Suntory Institute for Biomedical Research, 1-1-1 Wakayamadai. Shimamoto-cho, Mishima-gun, 618, Osaka, Japan

    Yoshihiro Tani, Kyoshi Saito, Atsuko Tsuneyoshi, Masahiro Imoto & Tomochika Ohno

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  1. Yoshihiro Tani
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  2. Kyoshi Saito
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  3. Atsuko Tsuneyoshi
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  4. Masahiro Imoto
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Tani, Y., Saito, K., Tsuneyoshi, A. et al. Nicotinic acetylcholine receptor (nACh-R) agonist-induced changes in brain monoamine turnover in mice. Psychopharmacology 129, 225–232 (1997). https://doi.org/10.1007/s002130050184

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  • DOI: https://doi.org/10.1007/s002130050184

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