Receptors with V1 characteristics mediate the maintenance of ethanol tolerance by vasopressin.
The neurohypophyseal hormone arginine vasopressin (AVP) acts in the central nervous system (CNS) to maintain functional tolerance to several effects of ethanol. The ability of exogenous vasopressin (administered i.c.v.) to maintain tolerance to the hypnotic effect of ethanol was blocked more effectively by antagonists acting at V1 receptors than by a V2-selective antagonist. Similarly, a V1-selective agonist was more potent than AVP in maintaining tolerance, whereas V2-selective agonists were inactive. These results indicate that vasopressin maintains ethanol tolerance via an action at CNS receptors that have the characteristics of V1 vasopressin receptors. Furthermore, a V1-selective antagonist, given alone, enhanced the rate of loss of tolerance, whereas a V2-selective antagonist did not, supporting a role for endogenous AVP, also acting at V1 vasopressin receptors, in the maintenance of ethanol tolerance. Characterization of the CNS receptors that mediate the modulation of ethanol tolerance by vasopressin suggests a mechanism of action of the peptide hormone in the CNS, and may contribute to the eventual development of therapies to modify functional ethanol tolerance.
Szabó
G
G
Laboratory of Physiologic and Pharmacologic Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.
Tabakoff
B
B
Hoffman
P L
PL
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003894:Deamino Arginine Vasopressin / Q000031:analogs & derivatives / Q000378:metabolism; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017483:Receptors, Vasopressin
D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000431:Ethanol; C007223:vasopressin, 1-deamino-4-Val-8-Arg-; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; C028884:1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-2-(O-ethyl-Tyr)-4-Val-arginine vasopressin; D003894:Deamino Arginine Vasopressin