Opiate and 5-HT 2A receptors in alcohol drinking: Preference in had rats is inhibited by combination treatment with naltrexone and amperozide

Abstract

Amperozide, a 5-HT 2A receptor antagonist, and naltrexone, an opiate receptor antagonist, have been shown to suppress volitional drinking of alcohol in experimental animals. The present study examined the effects of the concurrent administration of both drugs on the volitional intake of alcohol in the selectively bred, high alcohol drinking (HAD) rat. 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 maximally preferred concentration of 7% to 20% was offered to each HAD rat, amperozide and naltrexone were injected SC over a second 4-day period 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 naltrexone administered simultaneously at 1600 and 2200 h. Thereafter, alcohol preference testing continued for a third 4-day period. The alternate delivery of both drugs attenuated significantly the absolute g/kg and proportional intakes of alcohol in the HAD rats, whereas the saline vehicle was without effect. Although the simultaneous administration of naltrexone and amperozide produced an even greater decline in alcohol intake, without side effects on food and water intakes or on body weight, some residual drinking of alcohol persisted. Nevertheless, the results corroborate our previous findings on the suppression of alcohol drinking by antagonists of opiate and 5-HT 2A receptors. Because amperozide and naltrexone together reduce the apparent reinforcing property of alcohol, the theory is supported that the addictive liability to alcohol is underpined by multiple receptor subtypes within the mesolimbic and other systems in the brain.