Neuronal basis for the hyperthermic effect of mu-opioid agonists in rats: decrease in temperature sensitivity of warm-sensitive hypothalamic neurons.
The effect of the selective mu-opioid receptor agonist Tyr-Pro-N-MePhe-D-NH2 (PL-017) on tonic activity and temperature sensitivity of neurons in the preoptic area/anterior hypothalamus (PO/AH) has been examined in rat brain slices using extracellular recordings. The tonic activity of both warm-sensitive and temperature-insensitive neurons was inhibited in a dose-dependent manner by superfusion with the mu-agonist (0.5-100 nM). The temperature sensitivity was selectively decreased in warm-sensitive neurons in concentrations up to 10 nM. Only in the high concentration of 100 nM did the mu-agonist reduce the temperature coefficient of both types of neurons. Pretreatment with equimolar concentrations of the mu-antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) prevented the effects of the mu-agonist (0.5-10 nM) on tonic activity as well as temperature sensitivity. The results suggest that a specific change of the temperature sensitivity of PO/AH neurons is involved in the hyperthermia induced by mu-agonists in rats.
Yakimova
K S
KS
Department of Pharmacology, Faculty of Medicine, Sofia, Bulgaria.
Sann
H
H
Pierau
F K
FK
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
D004723:Endorphins; D017450:Receptors, Opioid, mu; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin; C044708:morphiceptin, N-Me-Phe(3)-