ELSEVIER PII S0031.9384(96)00049-X Physiology & Behavior, Vol. 60, No. 2, 439-446, 1996 Copyright © 1996 Elsevier Science Inc. Printed in the USA. All rights reserved 0031-9384/96 $15.00 + .00 Selective Effects of Naltrexone on Food Pleasantness and Intake MARTIN R. YEOMANS 1 AND RICHARD W. GRAY Laboratory of Experimental Psychology, University of Sussex, Brighton, BNq 9QG, UK Received 30 August 1995 YEOMANS, M. R. AND R. W. GRAY. Selective effects of nahrexone on food pleasantness and intake. PHYSIOL BEHAV 60(2) 439-446, 1996.--The effects of 50 mg naltrexone on both pleasantness and intake of 10 common food items were investigated using a double-blind placebo-controlled study with 16 male volunteers. Rated food pleasantness was reduced significantly in the naltrexone condition compared with both controls (placebo and baseline). However, pleasantness ratings were not affected uniformly across foods, with sweetened, fatty, and high-protein foods being most affected. Changes in rated unpleasantness generally mirrored those for pleasantness, but evaluations of saltiness and sweetness were unaffected by naltrexone. Although total intake was reduced in the naltrexone condition, this was not significant compared with placebo. However, fat and protein intakes were significantly less following naltrexone. The effect of naltrexone on intake was also food dependent, but in this case intake of sweet foods was spared relative to other food categories. The apparent discrepancy between liking and intake data with sweet foods could be interpreted in terms of the likely influence of normal eating styles on food selection during a buffet-style meal, and may explain some contradictions in previous studies of this kind. The implications for understanding opioid involvement in food acceptability are discussed. Feeding Naltrexone Palatability Opioids Human SEVERAL lines of evidence suggest that opioid peptides are involved in mediating the rewarding aspects of feeding, including evidence from animal studies that eating palatable foods causes opioid release (7). However, by far the most influential studies have examined the effects of opioid receptor antagonists both in animals and humans, and this article further evaluates the effects of one such antagonist, naltrexone, on a variety of measures of ingestion in human volunteers. Since the initial finding that naloxone reduces food intake in the rat (12), it has become widely accepted that opioid antago- nists reduce feeding in most species [see reviews (5,23)]. More- over, these effects appear to be driven primarily by reductions in meal size once feeding has started, rather than any reduction in motivation to initiate feeding (13). Consequently, research has concentrated on the nature of altered meal-taking following opi- oid antagonism, and a variety of evidence from studies in animals and humans using opiate antagonists has been used to support the idea that opioids play a role in orosensory reward mechanisms in feeding (14,15,28). For example, naloxone reduces sham-drink- ing of sweet solutions by rats (14). Because sham-feeding is believed to be driven primarily by orosensory reward, this clearly implicates opioids in reward. As well as animal studies supporting a role of opioids in the rewarding aspects of feeding, studies with humans have also been interpreted in this way. Initial investigations tended to examine the effects of naloxone (1,25) and naltrexone (20) on intake of single complex foods, and allowed little opportunity for dissocia- tion of the mechanisms underlying the observed anorectic effect. Subsequently, two different approaches have yielded data in support of a reward-based explanation. The first of these exam- ined the effects of naltrexone on hedonic evaluations of sweet solutions and food-related odours, and reported decreased liking for both sorts of stimuli following opioid blockade (8). With this dose of naltrexone (60 mg), it was suggested that the reduced liking for sweetness was independent of the effects of caloric preloading, because the alliesthesic effect of such preloads was maintained following naltrexone. However, more recent data suggest that low-dose naltrexone (25 mg) both reduces initial liking for sucrose and potentiates the alliesthesic effects of caloric preloads (18). Naltrexone has also been shown to reduce liking for more complex foods (3), and we have previously reported similar reductions in liking using the antagonist nalme- fene (27), a drug closely related to naltrexone. Thus, a variety of data suggest a specific role for opioid peptides in the mechanisms To whom requests for reprints should be addressed. 439