Decreased cerebral cortex and liver 5-HT2A receptor gene expression and enhanced ALDH activity in ethanol-treated rats and hepatocyte cultures

Abstract

Objective: In this work, we evaluated the differential binding of serotonin 2A (5-HT2A) receptor antagonist [3H](±)2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol] ([3H] MDL 100907) to 5-HT2A receptors in cerebral cortex and liver.Methods: Wistar adult male rats of 180–200 g body weight were given free access to 15% (v/v; ∼ 7·5 g/kg body weight per day) ethanol for 15 days. Brain 5-HT and its metabolites were assayed by a high-performance liquid chromatography. 5-HT2A receptor binding assay was done with different concentrations of [3H] MDL 100907. Hepatocyte culture was done with 10−9–10−3M of 5-HT and ketanserin. The hepatocytes were incubated for 24 hours at 37°C in 5% CO2.Results: Decreased 5-HT content (p<0·05 and p<0·001) and decreased (p<0·001) 5-HT2A receptor binding in cerebral cortex and liver of ethanol-treated rats were observed when compared with control. 5-HT2A receptor mRNA in the cerebral cortex and liver showed an increase in crossing threshold value showing decrease in gene expression in ethanol-treated rats when compared with control. In 24-hour culture works, hepatocytes with 10% ethanol showed an increase in aldehyde dehydrogenase (ALDH) activity (p<0·001), and it decreased (p<0·001) to a near-control level in the case of hepatocytes in a medium with 10% ethanol + 10−5M 5-HT and 10% ethanol + 10−7M 5-HT when compared with the hepatocytes in the medium with 10% ethanol.Conclusion: Our results suggest that the decreased serotonin function mediated through 5-HT2A receptors have a regulatory role on ALDH activity. This will have clinical significance to correct alcoholics from addiction due to allergic aldehyde accumulation.