OPIATE AND 5-HT2A RECEPTORS IN ALCOHOL-DRINKING - PREFERENCE IN HAD RATS IS INHIBITED BY COMBINATION TREATMENT WITH NALTREXONE AND AMPEROZIDE

Amperozide, a 5-HT2A receptor antagonist, and naltrexone, an opiate re ceptor antagonist, have been shown to suppress volitional drinking of alcohol in experimental animals. The present study examined the effect s of the concurrent administration of both drugs on the volitional int ake of alcohol in the selectively bred, high alcohol drinking (HAD) ra t. Individual preferences for alcohol were determined by a standard 10 -day test in which alcohol concentrations were increased from 3% to 30 %. Following a 4-day predrug test during which water together with a m aximally preferred concentration of 7% to 20% was offered to each HAD rat, amperozide and naltrexone were injected SC over a second 4-day pe riod as follows: 1) amperozide at 1600 h and naltrexone at 2200 h; 2) the same drugs but in reversed temporal order; and 3) amperozide and n altrexone administered simultaneously at 1600 and 2200 h. Thereafter, alcohol preference testing continued for a third 4-day period. The alt ernate delivery of both drugs attenuated significantly the absolute g/ kg and proportional intakes of alcohol in the HAD rats, whereas the sa line vehicle was without effect. Although the simultaneous administrat ion of naltrexone and amperozide produced an even greater decline in a lcohol intake, without side effects on food and water intakes or on bo dy weight, some residual drinking of alcohol persisted. Nevertheless, the results corroborate our previous findings on the suppression of al cohol drinking by antagonists of opiate and 5-HT2A, receptors. Because amperozide and naltrexone together reduce the apparent reinforcing pr operty of alcohol, the theory is supported that the addictive liabilit y to alcohol is underpined by multiple receptor subtypes within the me solimbic and other systems in the brain.