Peptides that regulate food intake: appetite-inducing accumbens manipulation activates hypothalamic orexin neurons and inhibits POMC neurons.

Corticolimbic circuits involving the prefrontal cortex, amygdala, and ventral striatum determine the reward value of food and might play a role in environmentally induced obesity. Chemical manipulation of the nucleus accumbens shell (AcbSh) has been shown to elicit robust feeding and Fos expression in the hypothalamus and other brain areas of satiated rats. To determine the neurochemical phenotype of hypothalamic neurons receiving input from the AcbSh, we carried out c-Fos/peptide double-labeling immunohistochemistry in various hypothalamic areas known to contain feeding peptides, from rats that exhibited a significant feeding response after AcbSh microinjection of the GABA(A) agonist muscimol. In the perifornical area, a significantly higher percentage of orexin neurons expressed Fos after muscimol compared with saline injection. In contrast, Fos expression was not induced in melanin-concentrating hormone and cocaine-amphetamine-related transcript (CART) neurons. In the arcuate nucleus, Fos activation was significantly lower in neurons coexpressing CART and proopiomelanocortin, and there was a tendency for higher Fos expression in neuropeptide Y neurons. In the paraventricular nucleus, no significant activation of oxytocin and CART neurons was found. Thus AcbSh manipulation may elicit food intake through coordinated stimulation of hypothalamic neurons expressing orexigenic peptides and suppression of neurons expressing anorexigenic peptides. However, activation of many neurons not expressing these peptides suggests that additional peptides/transmitters in the lateral hypothalamus and accumbens projections to other brain areas might also be involved.