DEVELOPMENT OF ALCOHOL TOLERANCE IN THE RAT AFTER A SINGLE EXPOSURE TO COMBINED TREATMENT WITH ARGININE(8)-VASOPRESSIN AND ETHANOL

A single i.c.v. injection of 100 ng of AVP, followed 30 min later by a n i.p. injection of EtOH (1.8 g/kg) and three 2-min trials of motor-im pairment testing on a moving bell, resulted in the development of tole rance to this effect of EtOH, that lasted up to 4 weeks. The rate of t olerance loss was not altered by daily injection of a V-1 receptor ant agonist, but pretreatment with a V-1 receptor antagonist or cyclohexim ide 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-dihydoxytryptamine also prevented the development of tolerance after a single exposure to AVP + EtOH, b ut the destruction of catecholamine terminals by i.c.v. injection of 6 -hydroxydopamine did not prevent such tolerance. In contrast to the fi ndings with motor impairment, no tolerance to EtOH-induced hypothermia and loss of righting reflex developed after a single combined AVP-EtO H 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.