Studies on the anticonvulsant effect of U50488H on maximal electroshock seizure in mice

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• 作者：Manocha ; Anshu ; Mediratta ; Pramod Kumari ; Sharma ; Krishna Kishore
• 关键词：U50488H ; Opioids ; Convulsions ; Maximal electroshock ; γ ; -Aminobutyric acid ; N-methyl-d-aspartate
• 刊名：Pharmacology Biochemistry and Behavior
• 出版年：2003
• 出版时间：August, 2003
• 年：2003
• 卷：76
• 期：1
• 页码：111-117
• 全文大小：177 K

文摘

The present study was designed to investigate the effect of U50488H, a prototype non-peptide kappa opioid agonist on convulsive behaviour using a maximal electroshock (MES) seizure test in mice. An attempt was also made to explore the role of possible receptors involved. MES seizures were induced via transauricular electrodes (60 mA, 0.2 s). Seizure severity was evaluated by means of two parameters, i.e., (1) duration of tonic hindlimb extensor phase and (2) mortality due to convulsions. Intraperitoneal (ip) administration of U50488H dose dependently (5–20 mg/kg) decreased the hindlimb extensor phase of MES. The anticonvulsant effect of U50488H was attenuated by the general opioid antagonist, naloxone at a high dose, and by MR2266, a selective kappa antagonist, but not by naltrindole, a delta antagonist. Coadministration of γ-aminobutyric acid (GABA)ergic drugs (diazepam, GABA, muscimol, and baclofen) and the N-methyl-d-aspartate (NMDA) receptor antagonist, dizocilpine (MK801), with U50488H augmented the anticonvulsant effect of the latter drug in mice. On the other hand, flumazenil, a central benzodiazepine (BZD) receptor antagonist, reversed the protective effect of diazepam and similarly, δ-aminovaleric acid (DAVA), a GABAub>Bub> receptor antagonist, blocked the protective effect of baclofen, a GABAub>Bub> agonist on the anti-MES action of U50488H. These BZD–GABAergic antagonists, namely, flumazenil or DAVA, on their own also counteracted the anti-electroshock seizure effect of U50488H given alone. However, mortality was not significantly altered in any of the above animal groups. Taken together, the findings have shown a possible role for multitude of important neurotransmitter systems, i.e., opioid (kappa), NMDA channel, GABAub>Aub>–BZD-chloride channel complex, and GABAub>Bub> receptors in the anticonvulsant action of U50488H.