Supraspinal, not spinal, alpha(2) adrenoceptors are involved in the anesthetic-sparing and hemodynamic-stabilizing effects of systemic clonidine in rats

Clonidine, an alpha(2) agonist, reduces the anesthetic requirement and atte nuates harmful hemodynamic responses to noxious stimuli. We examined the re sponsible sites of action in the central nervous system for the minimum alv eolar anesthetic concentration (MAC) and MAC blocking adrenergic response ( MAC-BAR) reducing effects of systemically administered clonidine in halotha ne-anesthetized rats. The MAC for halothane was determined by the tail clam p method, and MAC-BAR was defined as the MAC which attenuated hemodynamic r esponses within 10% after the tail clamp. We examined the effect of IV clon idine in the presence of rauwolscine, an alpha(2) antagonist given through IV, intrathecal (IT), intracisternal (IC), or intracerebroventrical (ICV) r outes. IV clonidine reduced MAC and MAC-BAR dose-dependently. IV and ICV ra uwolscine antagonized the MAC-reducing effect of clonidine, whereas IC and IT rauwolscine did not. In comparison, IV, ICV, and IC rauwolscine antagoni zed the MAC-BAR-reducing effect of clonidine; TT rauwolscine had no effect. Our data demonstrate that the alpha(2) adrenoceptors in the regions above mesencephalon and both the regions above mesencephalon and the lower brains tem are responsible for the MAC and MAC-BAR-reducing effect of systemic clo nidine in rats, respectively. However, the spinal a, adrenoceptors were not involved in these effects of clonidine. Implications: In the regions above mesencephalon, alpha(2) adrenoceptors were the most responsible for the mi nimum alveolar concentration-reducing effect and both the lower brainstem a nd regions above mesencephalon were involved in the minimum alveolar concen tration blocking adrenergic response-reducing effect of clonidine. The spin al alpha(2) adrenoceptors did not significantly contribute to these effects of clonidine.