GLUCOSE AND THE INSULIN-RELEASING DRUG TOLBUTAMIDE ATTENUATE THE EFFECTS OF MORPHINE AND ANGIOTENSIN ON ALCOHOL-CONSUMPTION

Animal studies have shown that insulin injections reduce alcohol intak e, implicating glucoregulatory processes in alcohol consumption. Angio tensin (ANG) II reduces alcohol intake and promotes glycogen breakdown in the liver but no studies have assessed the role of glucoregulatory processes in ANG II's effect. Similarly, glucose injections attenuate the analgesic and cognitive effects of opiates, yet no studies have a ssessed the effect of glucose on the well-documented ability of opiate s to enhance alcohol consumption. The present experiments further exam ine the role of glucoregulatory processes in alcohol intake by assessi ng the effect of glucose injections on morphine-enhanced alcohol consu mption and by evaluating the effect of the insulin-releasing drug, tol butamide, on ANG II-reduced alcohol consumption. Adult male Wistar rat s acquired alcohol drinking using the limited access procedure that of fers daily 40-min access to both 6% w/v alcohol and water and ensures reliable alcohol drinking in bouts large enough to produce pharmacolog ically relevant intakes. Experiment 1: after intake stabilized, four g roups of rats were first pretreated with vehicle injections and in the next phase, three of the four groups received either 50, 100, or 200 mg/kg glucose intraperitoneally (IP) prior to access to alcohol. Neith er the vehicle injections nor any of the glucose doses had an effect o n alcohol intake. In the final phase all groups continued to receive t heir respective glucose doses or vehicle but were now also treated wit h 5 mg/kg morphine sulphate LP prior to alcohol access. Morphine stimu lated alcohol intake to a similar degree in all groups except the 200 mg/kg group, which showed a significant attenuation in morphine-enhanc ed alcohol intake. Experiment 2: after intake stabilized, different gr oups of rats were pretreated with Vehicle injections and in the next p hase received either 5, 25, 50, or 100 mg/kg tolbutamide or vehicle su bcutaneously (SC) prior to alcohol access. The vehicle injections did not alter alcohol intake, and only the 100 mg/kg dose of tolbutamide p roduced a reduction in alcohol intake. In the final phase the groups c ontinued to receive their respective doses of tolbutamide or vehicle b ut were also treated with 400 mu g/kg ANG II SC immediately prior to a lcohol access. ANG II reduced alcohol intake to a similar extent in th e groups pretreated with 5-50 mg/kg tolbutamide. However, the 100 mg/k g dose of tolbutamide significantly attenuated ANG II's ability to red uce alcohol intake. These results demonstrate that manipulations that engage glucoregulatory processes can influence the mechanism(s) by whi ch morphine and angiotensin respectively increase and decrease alcohol drinking. Copyright (C) 1997 Elsevier Science Inc.