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Effects of Opioid and α2‐Adrenoceptor Agonists on the Isolated Ileum of Morphine‐dependent Guinea‐pigs During Withdrawal and After Clonidine Treatment

Abstract— The present study was undertaken to investigate the effect of clonidine administration to opiate‐dependent guinea‐pigs after morphine withdrawal on subsequent twitch responses of the longitudinal muscle‐myenteric plexus preparations to electrical field stimulation. The results indicate that clonidine, administered immediately after morphine removal, causes tolerance to the inhibition exerted by opioid and α2‐adrenoceptor agonists on the electrically‐evoked twitches. Such a finding suggests that the mechanism of action of clonidine involves not only its well‐known effects on locus coeruleus neurons but also that it has specific actions on the myenteric plexus. This work shows the existence of interactions between opioid and α‐adrenoceptor on the cholinergic neurons present in the isolated ileum.