Inhibition of clonic seizure-like excitatory effects induced by intrathecal morphine using two NMDA receptor antagonists: MK-801 and ACEA-1011.
Microinjection of high doses of morphine into the spinal lumbar intrathecal (i.t.) space of mice produces dose-dependent clonic seizure-like excitatory effects. Naloxone, an opioid antagonist (10 mg/kg, i.p.), injected 5 min prior to i.t. morphine, did not reverse the seizure-like motor effects, suggesting that these effects of morphine are not mediated through opioid receptors. Systemic administration of MK-801, a non-competitive NMDA receptor antagonist (0.01-0.10 mg/kg, i.p.), or ACEA-1011, a novel NMDA receptor/glycine site antagonist (0.5-20.0 mg/kg, i.p.), attenuated the clonic seizure-like excitatory effects induced by i.t. morphine in a dose-dependent manner. Sensorimotor performance of the mice was evaluated using the rotarod test. Although both compounds (MK-801 and ACEA-1011) impaired the sensorimotor performance of mice in a dose-dependent fashion, there was no impairment of motor performance at doses employed to block the excitatory effects induced by i.t. morphine. These data suggest that NMDA receptors play a pivotal role in the clonic seizure-like behaviors induced by i.t. morphine.
Lutfy
K
K
Department of Pharmacology, College of Medicine, UCI 92717.
Woodward
R M
RM
Keana
J F
JF
Weber
E
E
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects*; D009865:Oocytes; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D014982:Xenopus laevis
D000700:Analgesics; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C082999:ACEA 1011; D016291:Dizocilpine Maleate; D009020:Morphine