Opioid receptor mediation of the hypothermic response to caffeine.
Caffeine and other methylxanthines induce a dose-dependent reduction in core body temperature in mice. These experiments investigated the effects of neurotransmitter and neuromodulator antagonists on caffeine-induced hypothermia. Pretreatment with the alpha 2-adrenoceptor antagonist, atipamezole; the beta-adrenoceptor antagonist, propranolol; the dopamine antagonist, haloperidol; or the benzodiazepine receptor antagonist, flumazenil had no intrinsic effects on core body temperature nor did they interact significantly with the hypothermic effects of caffeine. The alpha 1-adrenoceptor antagonist, prazosin and the 5-HT receptor antagonist, metergoline significantly enhanced the hypothermic effects of caffeine, probably involving a combined effect with their intrinsic hypothermic actions. Pretreatment with the opiate receptor antagonist, naloxone (3 mg/kg i.p.), had no intrinsic effect on core body temperature but attenuated the hypothermic effect of caffeine reflected in a parallel shift to the right in the caffeine dose-effect curve. The naloxone-induced attenuation of the hypothermic effects of caffeine was also seen to be dose-dependent. The results reveal that opiate receptors (but not adrenoceptors, 5-HT, dopamine or benzodiazepine receptors) may play a role in modulating the hypothermic action of caffeine and possibly other methylxanthines.
Durcan
M J
MJ
Laboratory of Neurogenetics, DICBR, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
Morgan
P F
PF
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D011957:Receptors, Opioid / Q000502:physiology*; D013565:Sympatholytics / Q000494:pharmacology
D011957:Receptors, Opioid; D013565:Sympatholytics; D008711:Metergoline; D009270:Naloxone; D002110:Caffeine; D005442:Flumazenil