The Effect of Centrally Administered Glibenclamide, Tolbutamide and Diazoxide on Feeding in Rats.

While there are many theories on the control of feeding behavior that emphasize a role for energy substrates and their metabolism, the mechanism that couples changes in energy substrate supply and metabolism to alterations in food intake remains unclear. The purpose of the present project was to investigate the possibility that central ATP-sensitive potassium (KATP(+)) channels may serve as integrators between cellular energetics and alterations in neuronal activity that control feeding, such that pharmacologic manipulation of the channels would result in alterations in feeding behavior. Intracerebroventricular (ICV) injections of the KATP(+) channel blocker glibenclamide significantly increased feeding in fasted and fed male Sprague-Dawley rats. Likewise, the first generation sulfonylurea, tolbutamide, also increased feeding. ICV injection of the KATP(+) channel opener, diazoxide, modestly inhibited feeding. These results suggest that central KATP(+) channels may be involved in the regulation of feeding behavior.

ATP-sensitive K(+) Channels in the Regulation of Feeding Behavior: A Hypothesis.

In this paper we present a relatively narrow view of a wide body of literature, the elements of which share two featuresin common: an effect on food intake, and a relationship to an ATP-sensitive K(+) channel. With only sparse direct evidence available, we propose and provide circumstantial evidence supporting the hypothesis that ATP-sensitive potassium channels are ubiquitously relevant molecular integrators of energy balance, playing a role in numerous neuronal and hormonal systems involved in the maintenance of both energy intake and energy expenditure. Further, we focus on a few of the latest findings in this area which suggest that out hypothesis, while seemingly tenable, may involve process with unexpected levels of complexity.

Quinpirole-induced alterations of tail temperature appear as hyperalgesia in the radiant heat tail-flick test.

Several reports in the recent literature argue both for and against the importance of alterations of tail-temperature in the outcome of the tail-flick test. The data we present here support the assertion that drug-induced changes of tail-temperature may have a highly significant effect on tail-flick latency independent of drug-induced changes in nociception. We previously reported that peripherally administered injections of the dopamine agonist, quinpirole, produce significant reductions in the latency of response in the tail-flick test. This present work confirms our earlier findings; however, it indicates that the apparent hyperalgesia is an artifactual function of quinpirole-induced increases in tail temperature. Quinpirole (0.1-1.0 mg/kg I.P.) produced significant (p < 0.001), dose-dependent, and highly correlated increases in tail temperature and decreases in tail-flick latency 15 min following injection. When controls for the change in tail temperature were applied, there was no distinguishable effect of the drug on tail-flick latencies. Sixty minutes following the administration of quinpirole there was no observable effect of the drug on either tail-temperature or tail-flick latency. The results of this study indicate that a) peripherally administered quinpirole has no effect on nociception as measured in the tail-flick test apart from its ability to alter tail temperature; and b) alterations in tail temperature may significantly alter the outcome of the tail-flick test.

Dietary Sucrose Lowers Nociceptive Latencies Independently of Thermogenic Effects.

Previous reports indicate that chronic sucrose feeding produces a significant reduction in the latency of response in the radiant heat tail-flick test. Other earlier studies have shown a relationship between tail-skin temperature and tail-flick latency, while others yet have shown an increase in tail-skin temperature following sucrose feeding. Together these previous findings suggest the possibility that dietary-induced alterations in nociceptive latencies occur as an artifact secondary to diet-related changes in tail-skin temperature. The data presented in this study show that chronic sucrose feeding significantly increased tail-skin temperature (p < 0.0001) and decreased tail-flick latency (p < 0.0001) with significant correlations between tail-skin temperatures and tail-flick latencies in both the control and sucrose fed groups. However, while the slopes of the regression lines were similar for both groups, the elevations of the lines were significantly different (p = 0.0068) suggesting a dietary impact on nociceptive thresholds independent of the temperature effect. The data were also subjected to a previously reported temperature-correction procedure and comparisons in the methods of data analysis are discussed.