Assessment of alpha-2 adrenergic antagonists on the central nervous system using reticular contraction in sheep as a model

PL Toutain, MR Zingoni and Y Ruckebusch

In contrast to others species, the activity of ruminant forestomach (reticulum) is under the control of the central nervous system. Xylazine, a potent alpha-2 agonist, was shown to inhibit reticular activity. The potential usefulness of this physiological response to evaluate drugs acting on central adrenoreceptors was assessed. In conscious sheep, reticular activity was recorded either by electromyographic or manometric techniques. It was demonstrated that xylazine inhibited reticular contraction in a dose-dependent manner. This inhibition, which displayed limited intra- and intersubject variation, was related to a central action of xylazine because vagal stimulation was able to elicit reticular contraction. The so-called specific alpha-2 antagonists (tolazoline and yohimbine) or nonspecific (phentolamine) antagonists reduced xylazine inhibition. In contrast, the so-called alpha-1 antagonists (chlorpromazine, chlorprothixene, nicergoline, prazosin and thymoxamine) were without effect. Schild plots for the antagonists tolazoline and yohimbine in competition with xylazine were linear and had slopes that were not significantly different from unity, indicating competitive antagonism. These results suggest that reticular contractions, a discrete and periodic phenomenon of central origin easily recorded in conscious sheep, could be a useful physiological model to assess the effect of drugs on the adrenoreceptors of the central nervous system.

Volume 223, Issue 1, pp. 215-218, 10/01/1982
Copyright © 1982 by American Society for Pharmacology and Experimental Therapeutics