What we eat, when and how much, all are influenced by brain reward mechanisms that generate 'liking' and 'wanting' for foods. As a corollary, dysfunction in reward circuits might contribute to the recent rise of obesity and eating disorders. Here we assess brain mechanisms known to generate 'liking' and 'wanting' for foods, and evaluate their interaction with regulatory mechanisms of hunger and satiety, relevant to clinical issues. 'Liking' mechanisms include hedonic circuits that connect together cubic-millimeter hotspots in forebrain limbic structures such as nucleus accumbens and ventral pallidum (where opioid/endocannabinoid/orexin signals can amplify sensory pleasure). 'Wanting' mechanisms include larger opioid networks in nucleus accumbens, striatum, and amygdala that extend beyond the hedonic hotspots, as well as mesolimbic dopamine systems, and corticolimbic glutamate signals that interact with those systems. We focus on ways in which these brain reward circuits might participate in obesity or in eating disorders.

Orexin (hypocretin) is implicated in stimulating appetite as well as arousal, and in both food reward and drug reward. The ventral pallidum (VP) receives orexin projections from lateral hypothalamus neurons (LH), and orexin terminals are especially dense in the posterior half of VP, which is also the location of an opioid hedonic hotspot. The VP hotspot is a roughly cubic-millimeter site where mu opioid stimulation can amplify the hedonic impact of sweetness, expressed as an increase in 'liking' reactions to sucrose taste. The anatomical overlap in posterior VP between opioid hotspot and orexin inputs raises the possibility that the hedonic hotspot might allow orexin to amplify 'liking' too. We examined whether microinjections of orexin-A into the VP hotspot enhance the hedonic impact of sucrose, as assessed via affective taste reactivity measures of 'liking' reactions, and additionally compared effects at nearby sites in adjacent LH and extended amygdala. Taste reactivity results indicated that orexin stimulation specifically in the VP hotspot nearly doubled the magnitude of positive 'liking' reactions elicited by the taste of sucrose. Mapping results for localization of function, aided by Fos plume measures of the local spread of orexin impact, suggested that hedonic enhancement was generated by essentially the same cubicmillimeter of posterior VP previously identified as the opioid hotspot. By contrast, microinjection sites in the anterior half of VP, or in LH or extended amygdala, generally failed to produce any hedonic enhancement. We conclude that an orexin hedonic hotspot exists in posterior VP, with similar boundaries to the opioid hotspot. An orexin hedonic hotspot may permit regulatory hypothalamic circuitry to make foods more 'liked' during hunger by acting through VP. Dysfunction in a VP orexin hotspot in addiction or mood disorders might also contribute to some types of affective psychopathology.

Disgust is a prototypical type of negative affect. In animal models of excessive disgust, only a few brain sites are known in which localized dysfunction (lesions or neural inactivations) can induce intense ‘disgust reactions’ (e.g., gapes) to a normally pleasant sensation such as sweetness. Here we aimed to map forebrain candidates more precisely to identify where either local neuronal damage (excitotoxin lesions) or local pharmacological inactivation (muscimol-baclofen microinjections) caused rats to emit excessive sensory disgust reactions to sucrose. Our study compared subregions of nucleus accumbens shell, ventral pallidum, lateral hypothalamus and adjacent extended amygdala. Results indicated the posterior half of ventral pallidum to be the only forebrain site where intense sensory disgust gapes to sucrose were induced by both lesions and temporary inactivations (this site was previously identified as a hedonic hotspot for enhancements of sweetness ‘liking’). By comparison, for the nucleus accumbens, temporary GABA inactivations in the caudal half of the medial shell also generated sensory disgust but lesions never did at any site. Further, even inactivations failed to induce disgust in the rostral half of accumbens shell (which also contains a hedonic hotspot). In other structures, neither lesions nor inactivations induced disgust as long as the posterior ventral pallidum remained spared. We conclude that the posterior ventral pallidum is an especially crucial hotspot for producing excessive sensory disgust by local pharmacological/lesion dysfunction. By comparison, the nucleus accumbens appears to segregate sites for pharmacological disgust induction and hedonic enhancement into separate posterior versus rostral halves of medial shell.