Enhanced 5-HT(2A) receptor status in the hypothalamus and corpus striatum of ethanol-treated rats.
OBJECTIVE
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.


CONCLUSIONS
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.
Akash
K G
KG
Molecular neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682022 Kerala, India.
Balarama
K S
KS
Paulose
C S
CS
D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002492:Central Nervous System Depressants; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D012701:Serotonin; D000431:Ethanol; D006897:Hydroxyindoleacetic Acid; D007650:Ketanserin