Life Sciences, Vol. 37, pp. 2499-2505 Pergamon Press Printed in the U.S.A. NO IMPROVEMENTIN ETHANOL-INDUCEDMEMORY DEFICITS AFTER ADMINISTRATION OF A VASOPRESSINANALOG *Graeme Eisenhofer, David G. Lambie and Brian J. Robinson Wellington Clinical School of Medicine, Wellington Hospital, Wellington 2, New Zealand and *Building lO, Room 5N-214, National Institutes of Health, Betheda, Maryland 20892, United States of America (Received in final form October 14, 1985) Summary Acute ingestion of ethanol impairs memory, an effect which might be related to ethanol-induced inhibition of vasopressin release. This was studied using tests of memory and cognitive function in 26 normal subjects before and after ethanol ingestion. Equal numbers of subjects received randomly, by double-blind intranasal administration, placebo or 1-desamino-8- D-arginine vasopressin prior to ethanol ingestion. Administration of the vasopressin analog did not reverse the ethanol-induced deficits in memory and cognltive function. Vasopressin has been shown to improve memory consolidation in both vaso- pressin-deficient rats and control animals (1-3). A number of studies have also shown that vasopressin and some of its analogs improve learning and memory in cognitively impaired and in normal humans (4-15). Other studies have, however, shown no effect of vasopressin on memory in humans (16-19), although in some cases this may have been due to differences in dosage, route of administration or type of vasopressin analog used. Acute consumption of ethanol inhibits vasopressin release, an effect which is most pronounced in the early stages of intoxication, after which plasma vasopressin concentrations tend to return to baseline values despite the continuing presence of ethanol in the blood (20,21). Impairments of learning and memory occur after acute ingestion of ethanol (22-26), with greater cognitive impairment during the ascending as opposed to the descending limbs of the blood ethanol curve (24,27). Inhibition of vasopressin release might therefore be involved in the production of memory deficits after ethanol ingestion. In the present study we have examined memory function in normal subjects before and after ethanol ingestion, with and without administration of a vasopressin analog (1-desamino-8-D-arginine vasopressin, DDAVP). Methods Subjects. Fifteen men and eleven women, aged 18 to 41 yr (mean, 25.4 yr) and weighing 50-89kg (mean 68kg), participated in studies. Subjects refrained from eating and from drinking caffeinated beverages for 5 hr before study and 0024-3205/85 $3.00 + .00 Copyright (c) 1985 Pergamon Press Ltd.