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

Anesth Analg. 2000 Mar;90(3):722-6. doi: 10.1097/00000539-200003000-00039.


Clonidine, an alpha(2) agonist, reduces the anesthetic requirement and attenuates harmful hemodynamic responses to noxious stimuli. We examined the responsible sites of action in the central nervous system for the minimum alveolar anesthetic concentration (MAC) and MAC blocking adrenergic response (MAC-BAR) reducing effects of systemically administered clonidine in halothane-anesthetized rats. The MAC for halothane was determined by the tail clamp method, and MAC-BAR was defined as the MAC which attenuated hemodynamic responses within 10% after the tail clamp. We examined the effect of IV clonidine in the presence of rauwolscine, an alpha(2) antagonist given through IV, intrathecal (IT), intracisternal (IC), or intracerebroventrical (ICV) routes. IV clonidine reduced MAC and MAC-BAR dose-dependently. IV and ICV rauwolscine antagonized the MAC-reducing effect of clonidine, whereas IC and IT rauwolscine did not. In comparison, IV, ICV, and IC rauwolscine antagonized the MAC-BAR-reducing effect of clonidine; IT 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 brainstem are responsible for the MAC and MAC-BAR-reducing effect of systemic clonidine in rats, respectively. However, the spinal alpha(2) adrenoceptors were not involved in these effects of clonidine.

Implications: In the regions above mesencephalon, alpha(2) adrenoceptors were the most responsible for the minimum alveolar concentration-reducing effect and both the lower brainstem and regions above mesencephalon were involved in the minimum alveolar concentration blocking adrenergic response-reducing effect of clonidine. The spinal alpha(2) adrenoceptors did not significantly contribute to these effects of clonidine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology*
  • Anesthetics / pharmacology*
  • Animals
  • Brain / drug effects
  • Clonidine / administration & dosage
  • Clonidine / pharmacology*
  • Hemodynamics / drug effects*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha-2 / drug effects*
  • Receptors, Adrenergic, alpha-2 / physiology
  • Spinal Cord / drug effects*
  • Yohimbine / pharmacology


  • Adrenergic alpha-Agonists
  • Anesthetics
  • Receptors, Adrenergic, alpha-2
  • Yohimbine
  • Clonidine