A selective role for δ-receptors in the regulation of opioid-induced changes in seizure threshold

Abstract

In an effort to identify δ-receptor-specific properties for opioid modulation of seizure activity, studies were conducted with ICI 154,129, a putative δ-receptor antagonist, in the rat flurothyl test. Rats were pretreated i.c.v. with ICI 154,129 (50 μg) which, at this dose, does not alter normal seizure thresholds. Mean seizure thresholds for control groups (i.c.v. saline) ranged between 323–349 sec. In this test, D-Ala 2-D-Leu 5 enkephalin (20 μg, i.c.v.), metkephamid (40 mg/kg, s.c.), and etorphine (20 μg/kg, s.c.) raised seizure thresholds by 117, 128, and 140 % of control, respectively. Meperidine (25 mg/kg, s.c.) lowered seizure thresholds by 14 % less than control. Pretreatment with ICI 154,129 failed to antagonize the proconvulsant action of meperidine or the anticonvulsant and behavioral depressant actions of etorphine. The increases in seizure threshold produced by DADL and metkephamid (two δ-directed ligands) were significantly attenuated by ICI 154,129. However, the DADL-induced wet-shakes, rigid immobility, and behavioral depression were insensitive to ICI 154,129. These data indicate that ICI 154,129 possesses δ-receptor antagonistic to ICI 154,129. These in this in vivo model of seizure activity. Furthermore, since only the changes in seizure threshold were antagonized, it may be inferred that opioid-induced behavioral depression and DADLE wet-shakes are not a function of δ- receptor activity.