Mu, Delta and Kappa opioid receptor involvement in the hypothermic response to caffeine and theophylline

Abstract

This study describes the effect of the methylxanthines, caffeine and theophylline, on core body temperature (Tb); of unrestrained mice at normal ambient temperature. Acute administration (JP) of caffeine and theophylline produced a dose-dependent hypothermia; caffeine induced hypothermia war of a greater magnitude and longer time course than theophylline. The hypothermic response war attenuated (50%) by naloxone HCI, a peripheral and central non-selective opioid antagonist, showing that methylxamhine-induced hypothermia is partly mediated by opioid receptors. In part the hypothermic response appeared to be naloxone-insensitive (500A,) indicating that other mechanisms may mediate this effect. Only theophylline-treated mice exhibited an attenuation by 25% of this response when pretreated. with naloxone methiodide which only acts peripherally, indicating that part of the opioid receptor mediation of theophylline-induced hypothermia is dependent on a peripheral mechanism. No attenuation occurred when theophylline- and caffeine-treated mice were pretreated with low-dose naloxone Hel, a Mu- selective antagonist while naltrindole HCI. a Delta-selective antagonist produced a mild attenuation. The greater attenuation produced by nor-binaltorphimine, a Kappa-selective antagonist, would suggest that the Kappa receptors are mainly responsible for the opioid receptor mediation of both caffeine- and theophylline-induced hypothermia. The acute effects of caffeine and theophylline on thermoregulation are not unlike those of morphine and endogenous opioids. The pharmacological, clinical and biological significance of the thermoregulatory effects of caffeine and theophylline are discussed