Reduction of food intake and morphine analgesia by central glybenclamide.
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.
Roane
D S
DS
Division of Pharmacology and Toxicology, School of Pharmacy, NE Louisiana University, Monroe 71209-0470.
Boyd
N E
NE
D000255:Adenosine Triphosphate / Q000502:physiology; D000698:Analgesia; D000818:Animals; D004435:Eating / Q000187:drug effects*; D005905:Glyburide / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D015221:Potassium Channels; D009020:Morphine; D000255:Adenosine Triphosphate; D005905:Glyburide