Anticonvulsant Effects of Dadle are Primarily Mediated by Activation of Opioid Receptors: Interactions between and U Receptor Antagonists

摘要

Dose-response comparisons of the ability of the selective delta antagonist ICI 154, 129 (12.5-50 nmol), the nonselective antagonist naloxone (29-290 nmol), and the irreversible selective u antagonist B-fNA (1.3-21 nmol) to alter the threshold response to DADLE or etorphine was studied in the rat flurothyl seizure test. DADLE (35 nmol, i.c.v.) and etorphine (122 nmol/kg,s.c.) both caused increases in seizure threshold which were differentially antagonized by pretreatment (i.c.v.) with the respective antagonists. For DADLE, only ICI 154,129 and naloxone produced a dose-related blockade of the increase in seizure threshold, with ICI 154,129 being more potent than naloxone. In contrast, the anticonvulsant action of etorphine was not antagonized by ICI 154,129 (50 nmol), but was blocked by a low dose of naloxone (29 nmol) or B-fNA (21 nmol). In addition, prior occupancy of u-sites with beta-FNA (21 nmol) significantly diminished the abilities of eitherICI54,129 (50 nmol) of naloxone (290 nmol) to antagonize the anticonvulsant action of DADLE. The results of this study demonstrated that the effects of DADLE to increase seizure threshold in the rat were primarily mediated by activation of a delta-opioid receptor system. Furthermore, evidence has been provided for a functional interaction between delta and u receptors in the opioid regulation of seizure threshold.