Effect of conventional (mixed beta 1/beta 2) and novel (beta 3) adrenergic agonists on thermoregulatory behavior.
The effects of submaximal and maximal thermogenic doses of isoproterenol (ISO) on operant thermoregulatory responses in a cold (-8 degrees C) environment were tested in lean (+/?) Zucker rats trained to barpress for radiant heat. Contrary to expectations, ISO rats pressed for twice as much exogenous heat as controls, but showed a smaller rise in colonic temperature. Conversely, a beta 3-selective adrenergic agonist (RO40-2148) decreased the requirement for exogenous heat and produced larger rises in colonic temperature. RO40-2148 and another beta 3-agonist (ICI D7114) produced similar responses in obese (fa/fa) Zucker rats, but tests with ISO were terminated because it caused profound, and lethal hypothermia. The hypothermic effects of ISO on colonic temperature were also observed in Sprague-Dawley rats at room temperature (22 degrees C), whereas RO40-2148 produced hyperthermia. These results provide behavioral evidence for the high thermogenic selectivity of these novel adrenergic agonists and support the existence of an atypical beta 3-adrenoceptor. The hypothermic effects of ISO are presumed to be due to actions on beta 1- and/or beta 2-adrenoceptors.
Carlisle
H J
HJ
Department of Psychology, University of California, Santa Barbara 93106.
Stock
M J
MJ
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D005260:Female; D006358:Hot Temperature; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009930:Organic Chemicals; D010642:Phenoxyacetates / Q000494:pharmacology; D050198:Phenoxypropanolamines; D051381:Rats; D011919:Rats, Inbred Strains; D011924:Rats, Zucker
D000318:Adrenergic beta-Agonists; D009930:Organic Chemicals; D010642:Phenoxyacetates; D050198:Phenoxypropanolamines; C071909:ICI D7114; C073808:Ro 40-2148; D007545:Isoproterenol