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Reduction of food intake and morphine analgesia by central glybenclamide
1Division of Pharmacology and Toxicology, School of Pharmacy, NE Louisiana University, Monroe 71209-0470.
Abstract:
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.
Insights
The ATP-sensitive K+ channel (K+ATP) may link food intake and pain relief. Blocking K+ATP reduced food consumption and opioid-induced analgesia in rats, supporting its role as a common mediator.
Area of Science:
- Neuroscience
- Pharmacology
- Physiology
Background:
- A reciprocal relationship exists between food intake and opioid-mediated analgesia.
- The ATP-sensitive K+ channel (K+ATP) is a potential common mediator for ingestive and nociceptive behaviors.
- Opioid receptor agonists activate K+ATP channels for analgesia, while cellular ATP levels regulate channel closure.
Purpose of the Study:
- To investigate the role of the K+ATP channel in modulating the relationship between feeding and opioid function.
- To determine if K+ATP channel activity influences both food consumption and analgesia.
Main Methods:
- Administration of glybenclamide (a K+ATP antagonist) via the lateral ventricle in male Sprague-Dawley rats.
- Measurement of chow consumption over 48 hours post-administration.
- Assessment of analgesia using the tail-flick test following morphine sulfate administration.
Main Results:
- Glybenclamide administration significantly reduced chow consumption by up to 78% of control levels within 6 hours.
- Morphine sulfate produced significantly less analgesia in glybenclamide-treated rats compared to vehicle-treated controls (p < 0.05).
Conclusions:
- The results support the hypothesis that K+ATP channel activity is a key mediator in the reciprocal modulation of food intake and analgesia.
- The K+ATP channel represents a potential common cellular pathway for ingestive and nociceptive behaviors.