Yohimbine reduces morphine tolerance in guinea-pig ileum.
Opiates are known to inhibit electrically-evoked twitches of longitudinal muscle-myenteric plexus strips from guinea-pig ileum. When this preparation was incubated with morphine for 1 h tolerance developed to the inhibitory effect, since dose-response curves were shifted to the right. In the present study, the effects of alpha-2 adrenergic agents on the tolerance induced by morphine in this preparation was investigated. Addition of yohimbine 10 microM (but not 0.1 or 1 microM) to the incubating medium reduced the magnitude of opiate tolerance. This effect did not appear in the presence of the alpha-2 agonists clonidine or guanfacine (10 microM). Our results provide evidence of the longitudinal muscle-myenteric plexus as a useful model for the study of the relationship between morphine tolerance and alpha-2 adrenergic mechanisms.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004361:Drug Tolerance; D005260:Female; D016316:Guanfacine; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects; D010648:Phenylacetates / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology*
D006146:Guanidines; D010648:Phenylacetates; D015016:Yohimbine; D016316:Guanfacine; D009020:Morphine; D003000:Clonidine