INHIBITION OF THE ANTIANALGESIC ACTION OF DYNORPHIN-A IN MICE BY CHOLERA-TOXIN

Dynorphin A-(1-17) (Dyn A) administered intrathecally (IT) or released spinally in the mouse produces an antianalgesic action. The present e xperiments indicate that IT administration of cholera toxin inhibited the antianalgesic action of Dyn A. When clonidine was administered int racerebroventricularly (ICV) to release spinal Dyn A, IT cholera toxin inhibited the antianalgesic action of Dyn A so that the analgesic com ponent of action of clonidine became evident. Dyn A given IT inhibited the analgesic action of morphine given ICV. Cholera toxin given IT el iminated the antagonistic action of Dyn A. These results, in addition to others, indicate that IT cholera toxin antagonized the action of Dy n A. When the antianalgesic action of Dyn A was attenuated by pretreat ment with dynorphin antiserum or by pretreatment that produced desensi tization to Dyn A, cholera toxin had no effect. These results suggeste d that the antianalgesic action of Dyn A is mediated by activation of opioid receptors that are positively coupled to adenylate cyclase thro ugh a G(s) regulatory protein.