Effects of trimethyltin (TMT) on choline acetyltransferase activity in the rat hippocampus. Influence of dose and time following exposure

• Published in: Molecular and chemical neuropathology 1994-09, Vol.23 (1), p.27-45
• Main Authors: Cannon, R L, Hoover, D B, Baisden, R H, Woodruff, M L
• Format: Article
• Language: English
• Subjects: Animals; Choline O-Acetyltransferase - drug effects; Choline O-Acetyltransferase - metabolism; Dose-Response Relationship, Drug; Hippocampus - drug effects; Hippocampus - enzymology; Histocytochemistry; Male; Pyramidal Cells - drug effects; Pyramidal Cells - enzymology; Rats; Trimethyltin Compounds - pharmacology
• ISSN: 1044-7393
• DOI: 10.1007/BF02858505

Trimethyltin (TMT) destroys specific subfields of the hippocampus in the rat. TMT also increases choline acetyltransferase (ChAT) activity in CA1 of Ammon's horn and the outer molecular layer of the dentate gyrus. This observation suggests that axonal sprouting occurs in the cholinergic septohippocampal system in response to TMT. However, neither does-response nor time course data are available for the effects of TMT on this enzyme. The effects of three dose levels of TMT on ChAT activity in CA1 and the dentate gyrus were determined in Experiment 1 and ChAT activity in these two areas was measured at six time points following exposure to TMT in Experiment 2. Only the highest dose of TMT (6 mg/kg) significantly increased ChAT activity. ChAT activity in the dentate gyrus increased significantly by 3 d after administration and continued to increase until 21 d after exposure. A significant increase was not observed in CA1 until 7 d after exposure to TMT. Asymptotic levels were still reached at d 21. These results indicate a steep dose-response curve for TMT-induced changes in ChAT activity in the hippocampal formation and that this marker of cholinergic activity is more sensitive to perturbation by TMT in the dentate gyrus than Ammon's horn.