Development of alcohol tolerance in the rat after a single exposure to combined treatment with arginine8-vasopressin and ethanol.
A single i.c.v. injection of 100 ng of AVP, followed 30 min later by an i.p. injection of EtOH (1.8 g/kg) and three 2-min trials of motor-impairment testing on a moving belt, resulted in the development of tolerance to this effect of EtOH, that lasted up to 4 weeks. The rate of tolerance loss was not altered by daily injection of a V1 receptor antagonist, but pretreatment with a V1 receptor antagonist or cycloheximide prevented this AVP facilitation of the development of tolerance to EtOH-induced motor impairment. The destruction of serotonin neuronal terminals by i.c.v. injection of 5,7-dihydroxytryptamine also prevented the development of tolerance after a single exposure to AVP + EtOH, but the destruction of catecholamine terminals by i.c.v. injection of 6-hydroxydopamine did not prevent such tolerance. In contrast to the findings with motor impairment, no tolerance to EtOH-induced hypothermia and loss of righting reflex developed after a single combined AVP-EtOH treatment. The tolerance that develops after one treatment with AVP-EtOH is a functional rather than a dispositional tolerance, and shares many pharmacological properties with chronic tolerance to EtOH.
Wu
P H
PH
Department of Pharmacology, University of Toronto, Ontario, Canada.
Liu
J F
JF
Wu
W L
WL
Lança
A J
AJ
Kalant
H
H
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism
D004338:Drug Combinations; D001127:Arginine Vasopressin; D000431:Ethanol