THE REDUCTION IN ALCOHOL INTAKE BY THE 5-HT1A AGONIST 8-OH DPAT AND ITS ATTENUATION BY THE ALPHA(2) ADRENERGIC ANTAGONIST IDAZOXAN CORRELATES WITH BLOOD-GLUCOSE LEVELS

Serotonergic agents in general and the 5-HT1A agonist 8-OH DPAT in par ticular, reduce alcohol intake in rats and primates but the mechanism of this effect is not known. Previous studies have shown a correlation between alcohol consumption and the propensity to consume sweet subst ances. Indeed, certain biochemical events accompanying glucose utiliza tion have been proposed as satiety signals in the control of feeding, Since 8-OH DPAT produces hyperglycemia, we tested the hypothesis that its effect on alcohol intake may be partly mediated through an increas e blood glucose, Male Wistar rats were trained to drink a bout of 6% ( w/v) alcohol using the limited access procedure which offers a daily 4 0-min access to alcohol and water, On consecutive test trial days sepa rated by intervening non-drug days, the amount of alcohol consumed (1 g/kg on intervening days) was measured following the administration of X-OW DPAT (150 mu g/kg 10 min prior to drinking) alone or in combinat ion with the prior (20 min) injection of idazoxan (2 mg/kg), an alpha- 2 adrenoceptor antagonist with hypoglycemic properties. Idazoxan atten uated the hyperglycemic effect of 8-OH DPAT and completely reversed 8- OH DPAT's inhibitory effect on alcohol intake. Idazoxan alone produced a mild hypoglycemia and stimulated alcohol intake. These results supp ort a role for glucoregulatory processes in serotonergically-mediated changes in alcohol consumption.