Previous research has indicated the presence of a reciprocal relationship between food intake and opioid-mediated analgesia. We believe the cellular candidate most likely acting as a common mediator of both ingestive and nociceptive behaviors is the ATP-sensitive K+ channel (K+ATP). This ion channel appears to be opened by mu and delta 1 opioid receptor agonists in the service of analgesia, and closed as cellular ATP availability rises. To further examine the role of the K+ATP in the relationship between feeding and opioid function, we administered 80 nmol of glybenclamide (a K+ATP antagonist) to male SD rats via the lateral ventricle. Chow consumption in the treated animals was significantly reduced over the following 48 h (F = 2.62, p < 0.013), with the peak effect (78% of control) occurring at 6 h. In the tail-flick test, 4 mg/kg morphine sulfate provided analgesia of 42.38 +/- 8.4% and 18.89 +/- 7.67% in vehicle and treated animals, respectively (p < 0.05, n = 8/group, one-tailed t-test). These results support the hypothesis that food intake and analgesia are reciprocally modulated through activity at the K+ATP.