Effects of κ‐ and μ‐Selective Opiate Agonists on Colonic Temperature in Normoglycaemic and Streptozotocin‐Treated Hyperglycaemic Mice*

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Abstract
The thermic responses of highly selective κ‐(U‐69593 and U‐50488H) and μ(sufentanil and fentanyl) agonists were assessed in normoglycaemic and hyperglycaemic mice. Hyperglycaemia was induced by streptozotocin injection. The opiates were injected subcutaneously and colonic temperatures monitored for 90 min. after injection. In normoglycaemic animals the k‐agonists induced a significant hypothermic response and hyperglycaemia did not modify this effect. In normoglycaemic mice, low doses of μ‐selective agonists predominantly produced hypothermia, while in high doses resulted in hyperthermia. In chronic hyperglycaemic mice, hyperthermia was the predominant effect of μ‐opiates. The present results characterize the time couse and dose response of some of the currently available highly selective k‐ and μ‐opiate agonists for the first time in mice and suggest that hyperglycaemia differentially affects the opiate receptor subtypes that mediate thermoregulatory events.