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Investigations into the mechanism of reduction of ethanol sleep by thyrotropin-releasing hormone (TRH)

JM Cott, GR Breese, BR Cooper, S Barlow and AJ Prange

Thyrotropin-releasing hormone (TRH), administered intraperitoneally, was found to antagonize ethanol-induced sleep and hypothermia in mice without affecting brain ethanol content. This reduction of the actions of ethanol was also apparent after oral or intracisternal administration of TRH. In addition, TRH reduced ethanol-induced sleep in rats, hamsters, gerbils and guinea pigs. Evidence that the pituitary- thyroid axis is not necessary for the effects of TRH was provided by observations that hypophysectomy did not reduce TRH antagonism of ethanol narcosis and findings that neither triiodothyronine nor thyrotropin mimicked its action. Certain analogs of TRH, which have little effect on the pituitary, were also found to antagonize ethanol- induced sleep and hypothermia. Pretreatment with the antiadrenergic drugs, alpha-methyltyrosine, phentolamine and propranolol did not antagonize the ability of TRH to reduce sleep induced by ethanol. However, after intracisternal administration of atropine methyl nitrate, TRH no longer caused a significant reduction of sleep, even though TRH antagonism of the ethanol-induced hypothermia was still apparent. In contrast, central administration of other anticholinergic drugs, such as delta-tobocurarine and hexamethonium, reduced ethanol- induced sleep and this effect was additive with TRH. Carbachol also reduced ethanol sleeping time and this effect was also blocked by atropine methyl nitrate. The antagonism of ethanol-induced sleep by dibutyryl cyclic adenosine 3', 5'-monophosphate was significantly reduced but not blocked by atropine methyl nitrate. Results provide evidence that TRH has a direct extrapituitary action on brain and that both TRH and ethanol may interact with central cholinergic systems.

Volume 196, Issue 3, pp. 594-604, 03/01/1976
Copyright © 1976 by American Society for Pharmacology and Experimental Therapeutics




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T. Stanton, A. Bechman, and A Winokur
Thyrotropin-releasing hormone effects in the central nervous system: dependence on arousal state
Science, November 6, 1981; 214(4521): 678 - 681.
[Abstract] [PDF]

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L. Renaud, H. Blume, Q. Pittman, Y Lamour, and A. Tan
Thyrotropin-releasing hormone selectively depresses glutamate excitation of cerebral cortical neurons
Science, September 21, 1979; 205(4412): 1275 - 1277.
[Abstract] [PDF]


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Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics.