Neurons producing melanocortin receptor agonist, -MSH derived from proopiomelanocortin (POMC), and antagonist, agouti-related protein (AgRP), are known to be sensitive to metabolic stress such as food deprivation and glycoprivation. However, how these neurons respond to emotional/psychological stress remained to be elucidated. We report here that two acute emotional stressors, i.e. restraint and forced swim, evoked mRNA expression of c-fos, a neuronal activation marker, in a high percentage of POMC neurons (up to 53% for restraint stress and 62% for forced swim) with marked variations along the rostro-caudal axis of the arcuate nucleus. In contrast, only a small population of AgRP neurons in this brain region was activated. These neuronal activation patterns were correlated with behavioral reactions. Both stressors suppressed feeding and induced anxiety-like behavior in the elevated plus-maze test as reflected by a reduction in the percentage of entries and time spent in the open arms. Central pretreatment with SHU9119, a melanocortin receptor antagonist, dose-dependently attenuated the anorectic and anxiogenic effects elicited by acute restraint or forced swim. These results indicate that the melancortinergic pathway can be rapidly recruited by acute emotional stress, and that activation of melanocortin signaling is involved in mediating stress-induced anorexia and anxiety.