Decreased response to GABA-B agonists in longitudinal smooth muscle-myenteric plexus preparations from morphine-tolerant guinea-pigs.
1) Responsiveness of guinea-pig ileal longitudinal smooth muscle-myenteric plexus preparations to drugs activating GABA-B receptors was studied in morphine-tolerant animals. For this purpose morphine pellets (75 mg each) were implanted subcutaneously in guinea-pigs and experiments were performed three days later in electrically-stimulated ileal strips. 2) Activation of GABA-B receptors with GABA (10(-6) -10(-3) M) or (-)-baclofen (10(-6)-10(-3) M) caused a dose-related inhibition of twitch response that was about 80% lower in preparations from morphine-tolerant animals than in controls. This was found both in preparations maintained in the presence of morphine (10(-6) M) and in morphine-free Krebs. The effect was evident also in ileal preparations from morphine-tolerant animals in which a withdrawal syndrome was induced by the administration of naloxone before sacrifice. 3) The phenomenon was specific since the dose-response curve of the adenosine-inhibitory effect was comparable in preparations from tolerant animals and controls. 4) The hyporesponsiveness to GABA-B receptor activation began 12 h after pellet implantation and was maximal on the third day. 5) It is concluded that during tolerance to and withdrawal from morphine there is a hyporesponsiveness of GABA-B receptors in "in vitro" guinea-pig ileal longitudinal muscle-myenteric plexus preparations.
Luzzi
S
S
Department of Preclinical and Clinical Pharmacology Mario Aiazzi Mancini, University of Florence, Italy.
Franchi-Micheli
S
S
Ciuffi
M
M
Gori
A M
AM
Gentilini
G
G
Zilletti
L
L
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004558:Electric Stimulation; D006168:Guinea Pigs; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D009020:Morphine; D001418:Baclofen