Figure 2.

Melanocortins and the motivational basis of feeding. (a) Caloric insufficiency arising from energy expenditure creates a negative state of tension that represents caloric need and is interoceptively recognized as hunger. This caloric need (hunger) carries a negative valence that provides the motivation to rectify the homeostatic disturbance, which must also take into consideration other internal and external cues before initiating goal-directed food seeking and consumption. Food detection and caloric ingestion relieves the aversive state of hunger, reducing the initiating motivation, and thus satiety carries a positive valence. Experimental manipulation of melanocortinergic neurons bypasses the drive-reduction circuit and artificially creates the states of hunger (b) and satiety (c). (b) A perceived state of caloric need is created upon the activation of ARC^AgRP neurons or inhibition of PVH^MC4R neurons, artificially enhancing the motivation to consume food despite physiological caloric sufficiency. Consistent with the negative valence of hunger, the activation of ARC^AgRP neurons is aversive. (c) A perceived state of caloric sufficiency is created upon the inhibition of ARC^AgRP neurons or activation of PVH^MC4R neurons, artificially diminishing the motivation to consume food despite physiological caloric insufficiency. Consistent with the positive valence of satiety, the activation of PVH^MC4R(→LPBN) neurons or inhibition of ARC^AgRP neurons is appetitive. Red represents negative valence; green, positive valence. AgRP, agouti-related peptide; ARC, arcuate nucleus of the hypothalamus; MC4R, melanocortin-4 receptor; PVH, paraventricular nucleus of the hypothalamus.