alpha(2)-Adrenoceptor antagonists and propensity to take alcoholic beverages

Rats were maintained on a daily regimen involving a 2h opportunity to take both water and a sweetened alcoholic beverage (12% ethanol, 0.25% saccharin). After 3 weeks on this regimen, rats regularly take substantial amounts of alcohol. After stabilization, injections of alpha(2)-adrenergic antagonists were administered, 15min before the opportunity to drink. Yohimbine and methoxyidazoxan dose relatedly decreased intake of alcoholic beverage and increased intake of water. In Experiment 2, a number of rats were taken off the daily regimen for 9 days, then returned to it. Across the first 12 days of the reinstated daily regimen, half the rats received placebo and half methoxyidazoxan. The group receiving placebo rapidly returned to taking large amounts of alcoholic beverage while the group receiving methoxyidazoxan did not. In Experiment 3, it was shown that a dose of methoxyidazoxan that decreased intakes of alcoholic beverage did not decrease intakes of other palatable beverages. In Experiment 4, it was shown that yohimbine persistently reduced intakes of alcoholic beverage with daily administration. These results indicate that alpha(2)-antagonists might be effective pharmaceutical adjuncts to other treatments for alcohol abuse and alcoholism.