Pharmacological characterization of nicotinic acetylcholine receptor (nACh-R)-mediated acetylcholine release in rat brain

• Published in: Japanese Journal of Pharmacology Vol. 73; no. suppl.1; p. 88
• Main Authors: Yoshihiro Tani, Kyoshi Saito, Masahiro Imoto, Tomochika Ohno
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 1997
• ISSN: 0021-5198; 1347-3506

In vivo microdialysis technique was used to investigate nicotinic acetylcholine receptor (nACh-R)-mediated acetylcholine (ACh) release in the hippocampus, frontal cortex, and striatum of freely moving rats. Systemically administered (-)-nicotine (0.2, 1.0 and 5.0 mg/kg i.p.) significantly increased the release of ACh in the hippocampus and frontal cortex but not in the striatum. Dose-response curve of (-)-nicotine-induced ACh release was bell-shaped. In the hippocampus, the (-)-nicotine-induced increase of ACh release was blocked by pretreatment with the centrally acting nACh-R channel blocker mecamylamine (1.0 mg/kg i.p.) but not by hexamethonium (5.0 mg/kg i.p.), and (-)-cotinine (1.0 mg/kg i.p.) did not increase the ACh release, suggesting that the effects of (-)-nicotine were mediated by the central nACh-R, and the major metabolite of (-)-nicotine was not involved in the mediation of this response. (S)-3-methyl-5-(1-methyl-2-pyrrolidiny)isoxazole (ABT-418) (1.0 and 5.0 mg/kg i.p.), reported to show high affinity and selectivity for the α4β2 nACh-R subtype, also enhanced the release of ACh in the hippocampus, while 3-(2,4-dimethoxybenzlidene)-anabaseine (GTS-21) (1.0 and 5.0 mg/kg i.p.), high affinity for α7 nACh-R subtype, was without effect. These results indicate that there are certain differences among brain regions for the response of nACh-R-mediated ACII release and (-)-nicotine-induced ACh release in the rat hippocampus may be attributed to activation of the α4β2 nACh-R subtype but not the α7 nACh-R subtype.