Effect of mu-, kappa-, and delta-selective opioid agonists on thermoregulation in the rat.
The effect of selective mu-, kappa-, and delta-agonists on brain surface temperature (Tb), oxygen consumption (Vo2), and heat exchange (Q) was studied in unrestrained, male Sprague-Dawley rats using whole-body calorimetry. Hyperthermia, produced by PL-017 (1.86 nM) given ICV, resulted from increased Vo2 and reduced Q during the first 15-45 min postinjection. Tb returned to control levels due to a combination of increased Q and reduced Vo2. PL-017-induced hyperthermia was abolished by the mu-selective antagonist CTAP (0.75 nM). Dynorphin A1-17 (4.65 nM), a kappa-selective agonist, reduced both Vo2 and Q, resulting in hypothermia that was blocked by the kappa-selective antagonist nor-binaltorphimine (25 nM). The delta-selective agonist DPDPE (4.64 nM) caused no significant changes in Tb, Vo2, or Q. The data indicate that central stimulation of the mu- and kappa-opioid receptors affects both oxidative metabolism and heat exchange, which result in a change in Tb. These alterations can be prevented with selective opioid antagonist pretreatment.
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140.
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Handler
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Geller
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Adler
D000595:Amino Acid Sequence; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology; D004723:Endorphins / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008969:Molecular Sequence Data; D009019:Morphinans / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives*; D009292:Narcotic Antagonists / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000187:drug effects*; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects*
D004723:Endorphins; D004745:Enkephalins; D007211:Indoles; D009019:Morphinans; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009271:Naltrexone; D004399:Dynorphins; C044708:morphiceptin, N-Me-Phe(3)-; D020881:Enkephalin, D-Penicillamine (2,5)-; C055382:naltrindole