TEMPERATURE-DEPENDENT EFFECTS OF ALPHA-ADRENERGIC AGONISTS AND ANTAGONISTS IN THE COLD

This series of experiments examined whether temperature-dependent effects of the alpha-antagonists prazosin and yohimbine compromised their use as blockers of alpha-adrenergic agonist responses in cold-exposed rats. An operant leverpressing task was used to measure the demand for heat in a cold environment. The alpha(1)-antagonist prazosin had modest effects, but the alpha(2)-antagonist yohimbine was thermolytic in that it dose dependently increased operant responding but decreased posttest colonic temperature (Tc). These potent effects of the alpha(2)-antagonist led to tests of the alpha(2)-agonist clonidine. Clonidine increased operant responding for heat to an extraordinary degree, resulting in significant increases in posttest Tc. However, clonidine was found to be a hypothermic agent when tested in rats at 5 degrees C but denied the opportunity to increase body temperature by operant lever pressing, suggesting a central effect on the control of thermal balance. Measurement of changes in metabolic rate at 5 and 23 degrees C showed that yohimbine increased metabolism at 23 degrees C but decreased it in the cold. Prazosin had little effect on metabolism or Tc at either temperature. Prazosin inhibited the decrease in Tc induced by norepinephrine (NE), but had little effect on the lever-pressing response. Yohimbine had no significant antagonistic effect on NE-induced changes in lever-pressing behavior or posttest Tc, but neither did the thermolytic effects of yohimbine exacerbate those of NE. These results show that ct-antagonist interactions with agonists can be complicated by temperature-dependent effects of each.