Overlapping and interactive pathways regulating appetite and craving.

Multidisciplinary research in recent years has delineated the hypothalamic hardcore wiring that encodes appetitive drive. The appetite regulating network (ARN) consisting of distinct orexigenic and anorexigenic circuitries operates in the arcuate nucleus-paraventricular nucleus axis of the hypothalamus to propagate and relay the appetitive drive, and is subject to modulation by excitatory and inhibitory messages from the lateral hypothalamus and ventromedial nucleus, respectively. Reciprocal afferent humoral signals, comprised of anorexigenic leptin from white adipose tissue and orexigenic ghrelin from stomach, to the ARN integrate the moment-to-moment regulation of energy homeostasis. Various loci in the ARN and afferent hormonal feedback circuitry in the rodent brain are important for food craving elicited by drugs of abuse. This convergence of neurochemical and hormonal signaling has now paved the way to address the fundamental question of whether cellular and molecular events that underlie the appetitive drive in response to diminished energy stores in the body are akin to drug craving during withdrawal in humans.