Endogenous opioids encode relative taste preference Sharif A. Taha, 1,2 Ebba Norsted, 1,2 Lillian S. Lee, 1,2 Penelope D. Lang, 1,2 Brian S. Lee, 1,2 Joshua D. Woolley 1,2 and Howard L. Fields 1,2 1 Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, CA 94608, USA 2 Departments of Neurology and Physiology, and the Wheeler Center for the Neurobiology of Addiction, University of California, San Francisco, San Francisco, CA 94143, USA Keywords: food intake, nucleus accumbens, opioids, palatability, rat, ventral tegmental area Abstract Endogenous opioid signaling contributes to the neural control of food intake. Opioid signaling is thought to regulate palatability, the reward value of a food item as determined by orosensory cues such as taste and texture. The reward value of a food reflects not only these sensory properties but also the relative value of competing food choices. In the present experiment, we used a consummatory contrast paradigm to manipulate the relative value of a sucrose solution for two groups of rats. Systemic injection of the nonspecific opioid antagonist naltrexone suppressed sucrose intake; for both groups, however, this suppression was selective, occurring only for the relatively more valuable sucrose solution. Our results indicate that endogenous opioid signaling contributes to the encoding of relative reward value. Introduction A rich network of interrelated factors control feeding (Schwartz et al., 2000). These include the status of energy reserves, metabolic demand and the palatability of available foods. Of these, palatability is of particular interest because it plays an important role in driving caloric consumption in excess of metabolic demand, promoting obesity (Raynor & Epstein, 2001). Rats offered ad libitum access to a varied and palatable ‘cafeteria diet’ ingest many more calories than animals consuming nutritionally balanced but bland rat chow; indeed, cafeteria diets offer a well established paradigm for experimentally inducing obesity (Rogers & Blundell, 1984). Sensory attributes of palatable foods are generally those which signal high energy density, such as sweetness or fatty texture. Opioid signaling in the central nervous system plays a major role in neural processing related to palatability. Opioid agonists such as morphine potentiate food intake selectively, with the largest effects seen in consumption of palatable sweet or high-fat foods (Evans & Vaccarino, 1990). Nonspecific opioid antagonists such as naltrexone and naloxone suppress food intake, again with the largest effects evident during consumption of highly palatable food items (Le Magnen et al., 1980). These effects do not occur through modulation of postingestive feedback, as they are apparent even in sham-feeding rats (Rockwood & Reid, 1982). In addition, morphine administration increases positive facial reactivity displays, measures which are tightly correlated with food preference (Pecina & Berridge, 1995). These findings suggest a specific role for opioids in signaling the reinforcing value of palatable food items. The nucleus accumbens (NAcc) is a critical site of opioid signaling related to palatability. Infusion of naltrexone directly into the NAcc causes a selective decrease in sated rats’ sucrose intake, with minimal effects upon consumption of (less preferred) chow (Kelley et al., 1996). Conversely, infusion of the mu-opioid receptor (MOR) specific agonist [D-Ala2,N-Me-Phe4-Gly5-ol]-enkephalin (DAMGO) selec- tively increases intake of a variety of preferred substances, including sucrose, noncaloric saccharin and a dilute saline solution (Zhang & Kelley, 2002). These findings demonstrate an important role for NAcc opioid signaling in promoting consummatory behaviours related to preferred, highly palatable food items. The intrinsic sensory qualities of a particular food item are important determinants of its reward value, as measured by the food’s ability to motivate appetitive behaviour and to sustain consumption. In addition, when different foods are available, food-directed behaviours (both appetitive and consummatory) are typically guided by the relative value of competing food choices. A food item which is avidly consumed under normal conditions, for instance, may be rejected when more preferable alternatives are available (Brosnan & De Waal, 2003). Consummatory contrast paradigms provide well established behavioural models for manipulating the relative value of food rewards such as sucrose solutions (Flaherty, 1982). In anticipatory contrast paradigms, consumption of a palatable solution is suppressed by subsequent presentation of a second, more reinforcing, solution. This contrast effect is thought to develop through learned anticipation of the second solution (Flaherty & Checke, 1982; Flaherty & Rowan, 1985), and is dependent on the relative reward value of the contrasted solutions (Flaherty et al., 1994). We recently reported that a subset of NAcc neurons encode information related to the changing relative value of a sucrose solution modulated using a contrast paradigm (Taha & Fields, 2005). Because MOR agonists microinjected into the NAcc can increase consumption of palatable foods, we hypothesized that endogenous opioids contribute to this encoding and to consummatory behaviours guided by relative value. In the present study, an anticipatory contrast paradigm was used to modulate the relative value of an otherwise identical 4% sucrose solution in two groups of rats. Systemic administration of the nonspecific opioid antagonist naltrexone selec- tively reduced consumption of the relatively more palatable sucrose Correspondence: Dr Sharif A. Taha, 1 Ernest Gallo Clinic and Research Center, as above. E-mail: staha@phy.ucsf.edu Received 30 June 2005, revised 6 June 2006, accepted 8 June 2006 European Journal of Neuroscience, Vol. 24, pp. 1220–1226, 2006 doi:10.1111/j.1460-9568.2006.04987.x ª The Authors (2006). Journal Compilation ª Federation of European Neuroscience Societies and Blackwell Publishing Ltd