SUPPRESSION OF ALCOHOL PREFERENCE IN HIGH ALCOHOL-DRINKING RATS - EFFICACY OF AMPEROZIDE VERSUS NALTREXONE

The selectively bred high alcohol drinking (HAD) line of rat is consid ered as a potential model of one type of alcoholism. The purpose of th e present experiments was to compare the efficacy of two drugs on the volitional drinking of the HAD rats: the 5-HT2A receptor antagonist, a mperozide, and a nonselective antagonist of opiate receptors, naltrexo ne. To determine the pattern of alcohol drinking of the HAD rats, a st andard preference test was used in which water was offered with alcoho l increased in concentrations from 3% to 30% over 11 days. The maximal ly preferred concentration of alcohol of each rat was offered for 4 da ys and ranged from 7% to 20% with a mean intake of 6.9 g/kg per day. I nitially 1.0 mg/kg amperozide, 2.5 mg/kg naltrexone, or the saline veh icle were injected twice daily for 4 days at 1600 and 2200 hours. Seco ndly, 2.0 mg/kg amperozide, 5.0 mg/kg naltrexone, or the saline vehicl e were administered also for 4 days. After the drug sequences, alcohol preference tests continued for another 4 days. Whereas the saline veh icle was without effect on drinking, the administration of either drug caused a significant dose-dependent reduction in the daily intake of alcohol by the HAD vats in terms of absolute g/kg and proportion of al cohol to tenter consumed. A comparison of the drinking response to the higher doses of the two drugs showed that amperozide was move efficac ious in suppressing alcohol intake than naltrexone. Neither amperozide nor naltrexone exerted any significant effects on food and water inta kes or on body weight. These results support the concept of a function al link in the brain between the serotonergic and opioidergic systems postulated to underlie, in part, the aberrant drinking of alcohol. A m arked dissociation between the temporal patterns of drinking after nal trexone and amperozide treatment suggests that the opiate receptors me diate the immediate reinforcing effects of alcohol, whereas the more v egetative phenomena underlying addictive properties of alcohol are reg ulated by 5-HT2A receptors postsynaptic to serotonergic neurons. Final ly, the inhibitory actions of both drugs imply that multiple receptor mechanisms within the mesolimbic and other systems in the brain underp in the addictive liability to alcohol.