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.