ABSTRACT
In this work, the influences of CCK receptor antagonists on antinociception induced by the GABA receptor agonist, baclofen, and the GABA uptake inhibitor, THPO, in the formalin test have been studied. GABA-B agonist baclofen (0.75, 1.25 and 2.5 mg/kg), THPO, a GABA uptake inhibitor (1 and 2 mg/kg) and morphine (1.5, 3 and 6 mg/kg) induced antinociception in both phases of the formalin test in mice. The selective CCK receptor antagonists, L-365,260, MK-329 (0.05, 0.125 and 0.25 mg/kg) and non-selective CCK receptor antagonist, proglumide (2.5, 5, 10 and 20 mg/kg) induced antinociception only in high doses. The CCK receptor antagonists potentiated baclofen (0.75, 1.25 and 2.5 mg/kg) or THPO (1 and 2 mg/kg) responses. It may be concluded that the CCK receptor mechanism may interact with GABA-function in its antinociceptive effect.
Subject(s)
Analgesics, Non-Narcotic/pharmacology , GABA Agents/pharmacology , Pain Measurement/drug effects , Pain/physiopathology , Receptors, Cholecystokinin/antagonists & inhibitors , gamma-Aminobutyric Acid/physiology , Analgesics, Opioid/pharmacology , Animals , Baclofen/pharmacology , Dose-Response Relationship, Drug , Formaldehyde , GABA Agonists/pharmacology , GABA Antagonists/pharmacology , Injections, Intraperitoneal , Isoxazoles/pharmacology , Male , Mice , Morphine/pharmacologyABSTRACT
In this work, the influences of cholecystokinin receptor antagonists L-365,260, MK-329 and proglumide on antinociception induced by baclofen and GABA uptake inhibitor 4,5,6,7-tetrahydroisoxazolo [4,5-c]pyridin-3-ol (THPO) in the tail flick test has been studied. Baclofen and THPO induced antinociception in the tail flick test. Morphine, and the CCK receptor antagonists, MK-329, L-365,260 and proglumide also induced antinociception. The CCK receptor antagonists potentiated antinociceptive response induced by both baclofen and THPO. It may be concluded that cholecystokinin receptor mechanism(s) may interact with antinociception induced by GABA receptor mechanism(s).
Subject(s)
GABA Agonists/pharmacology , Pain Measurement/drug effects , Receptors, Cholecystokinin/antagonists & inhibitors , Animals , Baclofen/pharmacology , Benzodiazepinones/pharmacology , Devazepide/pharmacology , Dose-Response Relationship, Drug , Drug Interactions , Isoxazoles/pharmacology , Male , Mice , Motor Activity/drug effects , Pain/drug therapy , Phenylurea Compounds/pharmacology , Proglumide/pharmacology , TailABSTRACT
The effects of ethylketazocine, U-50,488, morphine and (-)-nicotine administered both i.p. and into the mid-fourth ventricle of intact rats were investigated using a conventional high intensity tail-flick reflex and one evoked with a lower intensity thermal stimulus. The sensitivity of the low intensity thermally evoked tail avoidance reflex was several times that of a high intensity tail-flick reflex in detecting the analgesic activity of morphine and yielded valid assays and relative potencies between morphine (1), EKC (18.76) and U-50,488 (0.23) when the drugs were administered ip. When the opioid drugs were administered into the fourth ventricle they produced a dose-related shortening of the latency of the low intensity thermally evoked tail avoidance reflex. (-)-Nicotine, when administered into the mid-fourth ventricle, produced analgesia in low doses and hyperalgesia in high doses. Naltrexone and mecamylamine, when administered into the fourth ventricle, produced a dose-related analgesia. Doses of naltrexone and mecamylamine which antagonize maximally hyperalgesic doses of (-)-nicotine and ethylketazocine did not produce analgesia; however, larger doses produced analgesia. These observations suggest that analgesic doses do not involve prototypic kappa opioidergic or nicotinic mechanisms. These data confirm the existence of a medullary hyperalgesic center which may have both mu and kappa opioidergic as well as nicotinic mechanisms. Furthermore, these data indicate that this medullary hyperalgesic mechanism may have spontaneous or evoked tone and provide an explanation for the analgesic action of naltrexone and mecamylamine.
