Involvement of NMDA receptors in thiopental-induced loss of righting reflex, antinociception and anticonvulsion effects in mice.
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.
Ge
Zhi Jun
ZJ
Department of Anesthesiology, Affiliated Hospital of First Clinical College, China Medical University, Shenyang, PR China.
Zhang
Li Cai
LC
Zeng
Yin Ming
YM
Da
Ti Jun
TJ
Wang
Jun Ke
JK
Cui
Guo Xin
GX
Tan
Yong Fei
YF
Zhao
Yan Ping
YP
Liu
Guo Jun
GJ
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*
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