MK-801, but not naloxone, attenuates high-dose dextromethorphan-induced convulsive behavior: Possible involvement of the GluN2B receptor

摘要

Abstract Dextromethorphan (DM) is a dextrorotatory isomer of levorphanol, a typical morphine-like opioid. When administered at supra-antitussive doses, DM produces psychotoxic and neurotoxic effects in humans. Although DM abuse has been well-documented, few studies have examined the effects of high-dose DM. The present study aimed to explore the effects of a single high dose of DM on mortality and seizure occurrence. After intraperitoneal administration with a high dose of DM (80mg/kg), Sprague–Dawley rats showed increased seizure occurrence and intensity. Hippocampal expression levels of N -methyl- d -aspartate (NMDA) receptor subunits (GluN1 Highlights ? High-dose (a supra antitussive dose) DM produces seizure behaviors. ? Intraperitoneal route (i.p.) is critical for induction of DM neurotoxicity. ? NMDA receptor antagonist, but not opioid receptor antagonist, attenuates DM seizures. ? GluN2B/NMDA signaling mediates DM-induced neurotoxicity.