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 µg i.c.v.) or bicuculline (0.6 µg 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.

Protective Effects of Sanjoinine A against N-Methyl-D-aspartate-Induced Seizure

“…Although it is still unclear from our data whether sanjoinine A exerts its antiseizure and neuron protective effects directly through NMDA receptors, it is possible that sanjoinine A may at least downregulate the excitatory effects of NMDA by stimulation of GABAergic systems. 41,[60][61][62] Sanjoinine A is effective in activating GABA A receptors, increasing GAD levels and increasing chloride influx in cultured neurons. 9) The chloride channel of the GABA A receptor is responsible for the rapid hyperpolarization, and activation of GABA A receptor could induce opening of chloride channel and subsequent hyperpolarization, which could block the excitatory effects induced by NMDA.…”

Protocatechuic acid ameliorates lipopolysaccharide‐induced kidney damage in mice via downregulation of TLR‐4‐mediated IKBKB/NF‐κB and MAPK/Erk signaling pathways

“…Mice were euthanized by cervical dislocation under light anesthesia by intraperitoneal injection of thiopental (50 mg/kg) (Ge et al, 2007). Kidney from each mouse was separated out and washed with phosphate buffer saline (PBS) to eliminate excess blood.…”

Drug Dependence Due to the Use of Barbiturates: The State of the Art

“…Анестетический эффект барбитуратов обусловлен снижением процессов возбуждения вследствие уменьшения проводимости ионов кальция: барбитураты инициируют приток ионов кальция, которые, в свою очередь, гиперполяризуют нейрон и блокируют тем самым проведение нервных импульсов [23][24][25][26][27][28][29][30][31][32][33]. В результате прием препаратов барбитуровой кислоты в невысоких дозах вызывает ощущение легкой эйфории, эмоциональную лабильность либо сонливость, ослабление чувства беспокойства.…”