Carlisle H J, Stock M J
Department of Psychology, University of California, Santa Barbara 93106, USA.
Pharmacol Biochem Behav. 1995 Jun-Jul;51(2-3):263-70. doi: 10.1016/0091-3057(94)00374-r.
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 alpha-antagonist interactions with agonists can be complicated by temperature-dependent effects of each.
这一系列实验研究了α-拮抗剂哌唑嗪和育亨宾的温度依赖性效应是否会影响它们在冷暴露大鼠中作为α-肾上腺素能激动剂反应阻滞剂的应用。采用操作性杠杆按压任务来测量寒冷环境中对热量的需求。α1-拮抗剂哌唑嗪的作用较小，但α2-拮抗剂育亨宾具有致热分解作用，即它剂量依赖性地增加操作性反应，但降低测试后结肠温度（Tc）。α2-拮抗剂的这些强效作用促使对α2-激动剂可乐定进行测试。可乐定极大地增加了对热量的操作性反应，导致测试后Tc显著升高。然而，当在5摄氏度的大鼠中进行测试但没有通过操作性杠杆按压来升高体温的机会时，发现可乐定是一种体温降低剂，这表明其对热平衡控制有中枢作用。在5摄氏度和23摄氏度下测量代谢率变化表明，育亨宾在23摄氏度时增加代谢率，但在寒冷环境中降低代谢率。哌唑嗪在这两个温度下对代谢率或Tc几乎没有影响。哌唑嗪抑制去甲肾上腺素（NE）诱导的Tc降低，但对杠杆按压反应几乎没有影响。育亨宾对NE诱导的杠杆按压行为变化或测试后Tc没有显著拮抗作用，而且育亨宾的致热分解作用也没有加剧NE的作用。这些结果表明，α-拮抗剂与激动剂的相互作用可能会因各自的温度依赖性效应而变得复杂。
