title: Involvement of NMDA receptors in thiopental-induced loss of righting reflex, antinociception and anticonvulsion effects in mice.
abstract: Potentiation of GABA(A) receptor-mediated inhibitory neurotransmission contributes to the anesthetic action of thiopental. However, the inhibiting action of general anesthetic on excitatory neurotransmission also purportedly underlies its effects. The aim of the study was to elucidate the role of glutamate receptors (NMDA and AMPA receptors) in thiopental-induced anesthesia. Intracerebroventricular (i.c.v.) NMDA (50 ng) significantly increased the induction time of loss of righting reflex and decreased sleep time induced by intraperitoneal injection (i.p.) of thiopental (50 mg/kg). Furthermore, NMDA at 50 ng i.c.v. increased the 50% effective dose values for thiopental to produce loss of righting reflex and immobility in response to noxious tail clamp by 25% and 21% (p < 0.05), respectively. However, intrathecal (IT) administration of NMDA or both of i.c.v. or IT administration of AMPA did not show such antagonizing effects on thiopental action at subconvulsive dose. Finally, thiopental (25 mg/kg i.p.) inhibited convulsions induced by NMDA (0.4 microg i.c.v.) or bicuculline (0.6 microg i.c.v.). However, i.p. muscimol (1 mg/kg) blocked the convulsions induced by bicuculline, but not those induced by NMDA at 3 mg/kg. Similarly, i.p. MK-801 (0.1 mg/kg) antagonized NMDA-induced convulsions, but not bicuculline-induced convulsions at 0.3 mg/kg. Therefore, we suggest that the effects of the selective GABA(A) and NMDA receptors on convulsive behavior are special to their sites of action, and that the inhibitory action of thiopental on NMDA receptors is possibly not mediated by secondary effects of its GABA(A) receptors agonism. These results above indicate the involvement of NMDA receptors in thiopental-induced anesthesia in mice.
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of First Clinical College, China Medical University, Shenyang, PR China.
authors.forename: Zhi Jun
authors.initials: ZJ
authors.lastname: Ge
authors.forename: Li Cai
authors.initials: LC
authors.lastname: Zhang
authors.forename: Yin Ming
authors.initials: YM
authors.lastname: Zeng
authors.forename: Ti Jun
authors.initials: TJ
authors.lastname: Da
authors.forename: Jun Ke
authors.initials: JK
authors.lastname: Wang
authors.forename: Guo Xin
authors.initials: GX
authors.lastname: Cui
authors.forename: Yong Fei
authors.initials: YF
authors.lastname: Tan
authors.forename: Yan Ping
authors.initials: YP
authors.lastname: Zhao
authors.forename: Guo Jun
authors.initials: GJ
authors.lastname: Liu
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D008297:Male; D051379:Mice; D009068:Movement / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D016202:N-Methylaspartate; D010147:Pain Measurement; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012021:Reflex, Abnormal / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D013874:Thiopental / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D018686:Anesthetics, Intravenous; D000927:Anticonvulsants; D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D009118:Muscimol; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D013874:Thiopental; D001640:Bicuculline