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Enhanced 5-HT2A Receptor Status in the Hypothalamus and Corpus Striatum of Ethanol-Treated Rats

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Abstract

Aim Brain is the major target for the actions of ethanol and it can affect the brain in a variety of ways. In the present study we have investigated the changes in 5-HT level and the 5-HT2A receptors in the ethanol-treated rats. Methods Wistar adult male rats of 180–200 g body weight were given free access to 15% (v/v) (approx.7.5 g/Kg body wt./day) ethanol for 15 days. Controls were given free access to water for 15 days. Brain 5-HT and its metabolites were assayed by high performance liquid chromatography (HPLC) integrated with an electrochemical detector (ECD) fitted with C-18-CLS-ODS reverse phase column. 5-HT2A receptor binding assay was done with different concentrations of [3H] MDL 100907. Results The hypothalamic 5-HT content significantly increased (P < 0.001) with a decreased (P < 0.001) 5-HIAA/5-HT turnover in the ethanol-treated rats when compared to control. The corpus striatum 5-HT content significantly decreased (P < 0.01) with increased (P < 0.01) 5-HIAA/5- HT turnovers in the ethanol-treated rats when compared to control. Scatchard analysis of [3H] MDL 100907 against ketanserin in hypothalamus showed a significant increase (P < 0.001) in Bmax with a decreased affinity (P < 0.001) in ethanol-treated rats when compared to control. The competition curve for [3H] MDL 100907 against ketanserin fitted one-site model in all the groups with unity as Hill slope value. An increased Ki and log (EC50) value were also observed in ethanol-treated rats when compared to control. Scatchard analysis of [3H] MDL 100907 against ketanserin in the corpus striatum of ethanol-treated rats showed a significant increase (P < 0.001) in Bmax and in affinity (P < 0.01) when compared to control. The change in affinity of the receptor protein in both corpus striatum and hypothalamus shows an altered receptor. The competition curve for [3H] MDL 100907 against ketanserin fitted one-site model in all the groups with unity as Hill slope value. There was no significant change in Ki and log (EC 50) value in ethanol-treated rats when compared to control. Conclusion The present study demonstrated the enhanced 5-HT2A receptor status in hypothalamus and corpus striatum. The ethanol-induced enhanced 5-HT2A receptors in the hypothalamus and corpus striatum has clinical significance in the better management of ethanol addiction. This will have therapeutic application.

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Acknowledgement

This work was supported by research grant from ICMR, DBT, DAE, DST, Government of India to Dr. C. S. Paulose.

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  1. Molecular neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682 022, Kerala, India

    K. G. Akash, K. S. Balarama & C. S. Paulose

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  1. K. G. Akash
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Akash, K.G., Balarama, K.S. & Paulose, C.S. Enhanced 5-HT2A Receptor Status in the Hypothalamus and Corpus Striatum of Ethanol-Treated Rats. Cell Mol Neurobiol 28, 1017–1025 (2008). https://doi.org/10.1007/s10571-008-9281-2

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