Orexin neurons in the lateral hypothalamus (LH) send projections to reward-associated brain areas including the nucleus accumbens and the ventral tegmental area (VTA), indicating a possible mechanism whereby LH stimulation could influence motivated behavior. Last year we reported that LH orexin neurons are stimulated (as measured by Fos induction) in proportion to the amount of preference shown for food-, cocaine- or morphine-associated cues during conditioned place preference (CPP) testing (Harris et al., SFN 2004). These findings were specific for orexin neurons located lateral to the fornix in the LH area but not for orexin neurons found medial to or surrounding the fornix. This data indicated that activation of orexin cells in the LH maybe involved in the preference (or craving) for reward-related cues. In the current studies, we found that microinjections of Y4 agonist, rat pancreatic polypeptide rPP, a potent stimulator of orexin cells; 0.045 nmol/side) into the LH reinstated an extinguished CPP for ...