Arginine-8-vasopressin potentiates acute ethanol intoxication.
AVP maintains ethanol (EtOH) tolerance after cessation of chronic EtOH treatment. However, the acute interaction of AVP and EtOH has not been well characterized. Rats were trained on a moving belt and the EtOH dose-response relationship (range 1.0-2.0 g/kg) was determined after pretreatment with saline, AVP (2.5-40 micrograms SC or 10 ng ICV), the AVP-V1 receptor antagonist [Des-Gly9,d(CH2)5(1),O-Et-Tyr2, Val4,Arg8]-vasopressin (10 ng ICV), or AVP in combination with the V1 antagonist. AVP produced a 16% decrease in the EtOH ED50 when given either SC or ICV; this decrease, which appears to represent true potentiation rather than additivity, was prevented by the preadministration of the V1 antagonist. Other rats were made EtOH-tolerant by 7 daily injections of either EtOH alone (1.8 g/kg IP) or EtOH (1.5 g/kg IP) + AVP (10 micrograms SC), followed by a practice session on the moving belt. In both sets of tolerant animals, AVP potentiation of acute EtOH effects was still seen on day 6. The mechanism of AVP potentiation of EtOH-induced impairment is unknown, but the failure of the V1 antagonist alone to alter the effect of EtOH suggests that endogenous AVP is not involved directly in modulating EtOH intoxication.
Wu
P H
PH
Department of Pharmacology, Faculty of Medicine, University of Toronto, Ontario, Canada.
Liu
J F
JF
Mihic
S J
SJ
Kalant
H
H
D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004361:Drug Tolerance; D000431:Ethanol / Q000097:blood; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D001127:Arginine Vasopressin; D000431:Ethanol