K G Akash1, K S Balarama, C S Paulose. 1. Molecular neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682022 Kerala, India.
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-HT(2A) 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-HT(2A) 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 [(3)H] MDL 100907 against ketanserin in hypothalamus showed a significant increase (P < 0.001) in B(max )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 K(i) and log (EC(50)) 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 B(max) 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 [(3)H] MDL 100907 against ketanserin fitted one-site model in all the groups with unity as Hill slope value. There was no significant change in K(i) and log (EC (50)) value in ethanol-treated rats when compared to control. CONCLUSION: The present study demonstrated the enhanced 5-HT(2A) receptor status in hypothalamus and corpus striatum. The ethanol-induced enhanced 5-HT(2A) receptors in the hypothalamus and corpus striatum has clinical significance in the better management of ethanol addiction. This will have therapeutic application.
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-HT(2A) 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-HT(2A) 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 [(3)H] MDL 100907 against ketanserin in hypothalamus showed a significant increase (P < 0.001) in B(max )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 K(i) and log (EC(50)) 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 B(max) 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 [(3)H] MDL 100907 against ketanserin fitted one-site model in all the groups with unity as Hill slope value. There was no significant change in K(i) and log (EC (50)) value in ethanol-treated rats when compared to control. CONCLUSION: The present study demonstrated the enhanced 5-HT(2A) receptor status in hypothalamus and corpus striatum. The ethanol-induced enhanced 5-HT(2A) receptors in the hypothalamus and corpus striatum has clinical significance in the better management of ethanol addiction. This will have therapeutic application.
Authors: D Hoyer; D E Clarke; J R Fozard; P R Hartig; G R Martin; E J Mylecharane; P R Saxena; P P Humphrey Journal: Pharmacol Rev Date: 1994-06 Impact factor: 25.468
Authors: Mangatt P Biju; Sulaiman Pyroja; Neelimmathara V Rajeshkumar; Cheramadathikudyil S Paulose Journal: Neurochem Res Date: 2002-09 Impact factor: 3.996