Orexin A in the nucleus accumbens stimulates feeding and locomotor activity.

Due to the nature of processing within the accumbens shell (AccSh) and the presence of orexin receptors and varicosities within the AccSh, we hypothesized that orexin A may partly regulate feeding behavior and locomotor activity via signaling in this site. To test this hypothesis, male Sprague-Dawley rats were implanted with guide cannulae directed to the medial portion of the AccSh. Orexin A (0, 100, 500, and 1000 pmol, in 0.5 microl artificial cerebrospinal fluid) was infused into the AccSh and feeding behavior and locomotor activity were monitored. The effect of pretreatment with an orexin 1 receptor antagonist (SB334867A) on orexin A-induced feeding and locomotor activity was assessed. Orexin A augmented feeding in the 0-1 h and 1-2 h post-infusion interval (P = 0.0058 and P = 0.025, respectively) and stimulated locomotor activity in the 30-60 min, 60-90 min, and 90-120 min post-infusion intervals (P <or= 0.0001, P = 0.0056 and P = 0.046, respectively). Orexin A-induced feeding was significantly attenuated by preadministration of SB334867A in the 0-1 h post-infusion time interval (P = 0.03). Orexin A-induced locomotor activity was not affected by SB334867A. These data support the hypothesis that the AccSh is a site of orexin A modulation of feeding behavior and locomotor activity.