Opiate-induced seizures: A study of μ and δ specific mechanisms

Abstract

Two groups of experiments were conducted to determine if morphine- and enkephalin-induced seizures are specifically mediated by the μ and δ receptor, respectively. In the first experiments, designed to assess the ontogeny of μ- or δ-seizures, rats from 6 h to 85 days of age received implanted cortical and depth electrodes as well as an indwelling cannula in the lateral ventricle. Various amounts of the μ-receptor agonists, morphine and morphiceptin, and the δ agonists, d-Ala 2- d-Leu 5-enkephalin (DADL) and Tyr- d-Ser-Gly-Phe-Leu-Thr (DSLET), were then administered intracerebroventricularly (icv) with continuous EEG monitoring. The second experiments entailed use of the nonspecific opiate antagonist, naloxone, as well as the specific δ antagonist, ICI 154,129, against seizures induced by icv-administered morphine, morphiceptin, DADL, or DSLET. Both morphine and morphiceptin produced electrical seizure activity in rats as young as 5 days after birth. The drugs produced similar seizure activity in terms of electrical morphology, observed behavior, ontogeny, threshold dose, and reversibility with small doses of naloxone. In the pharmacologic experiments, icv naloxone blocked all opiate-induced seizures. ICI 154,129 blocked DSLET seizure, had little effect on enkephalin or DADL seizures, and no effect on morphine or morphiceptin seizures. These data indicate that DSLET seizures are δ-specific but that all other opiate-induced seizures studied may involve multiple opiate receptor-mediated mechanisms.