Effect of p-coumaric acid on olfactory bulbectomy induced depression-like behaviors and its AMPA receptor mechanism in mice / 中国药理学通报

Aim To investigated the effect of p-CA on depression-like behaviors of mice of olfactory bulbectomy and its possible mechanism. Methods The olfactory bulbectomy (OBX) model of mice was established by an operation of olfactory bulbectomy. The behaviors of the mice were detected by the forced swimming test and the tail suspension test. Results The depression-like behavior in the forced swimming and tail suspension test and the in the open field test significantly increased in OBX mice; however, p-CA improved the depres- sion-like behavior in the forced swimming and tail sus pension test and the hyper-locomotor activity in open field test in OBX mice. Moreover, treatment with AMPA receptor antagonist NBQX blocked this improving effect of p-CA. While, treatment with AMPA receptor agonist CX546 enhanced this improving effect of p-CA. Conclusions P-CA improves depression-like behaviors of OBX mice, and AMPA receptors may mediate this effect.

Antinociceptive Interactions between Intrathecal Gabapentin and MK801 or NBQX in Rat Formalin Test

Antagonists for spinal N-methyl-D-aspartate (NMDA) and amino-hydroxy-methtyl-isoxazolepropionate (AMPA) receptors are effective in attenuating acute nociception or injury-induced hyperalgesia. The antinociception of spinal gabapentin is developed in injury-induced hyperalgesia without affecting acute nociception. The authors evaluated the effects of intrathecal gabapentin, NMDA antagonist (MK801) and AMPA antagonist (NBQX) in the formalin test which shows injury-induced hyperalgesia as well as acute pain. We further assessed the interactions between gabapentin and either MK801 or NBQX. Male Sprague-Dawley rats were implanted with intrathecal catheters. To evoke pain, 50 microliter of 5% formalin solution was injected into the hindpaw. The interaction was investigated by a fixed dose analysis or an isobolographic analysis. MK801 and NBQX suppressed flinching responses during phase 1 of the formalin test, while gabapentin had little effect on phase 1. All three agents decreased the phase 2 flinching response. A fixed dose analysis in phase 1 showed that gabapentin potentiated the antinociceptive effect of MK801 and NBQX. Isobolographic analysis in phase 2 revealed a synergistic interaction after coadministration of gabapentin-MK801 or gabapentin-NBQX. Correspondingly, spinal gabapentin with NMDA or AMPA antagonist may be useful in managing acute pain and injury-induced hyperalgesia.

The Effects of Intrathecal Ketamine and NBQX on Neurologic Injury and Spinal Cord Glutamate Receptor mRNA Expression in Transient Spinal Ischemia in the Rat / 대한구급학회지

BACKGROUND: Spinal cord injury occurring as the result of surgical repair of thoracic and thoracoabdominal aortic disease remains a devastating complication. Excitatory amino acids have been known to cause neurologic injury after neuronal ischemia. The purpose of this study was to elucidate the effects of intrathecal ketamine or NBQX on neurologic outcome and NMDA receptor gene expression in transient spinal ischemia. METHODS: Sprague-Dawley rats were anesthetized with enflurane, divided by 4 groups: Control (C group), Intrathecal ketamine 0.1 mg (K-1 group), Intrathecal ketamine 0.2 mg (K-2 group), and intrathecal NBQX 1 nM (N group). Spinal ischemia was produced by both induced hypotension and thoracic aortic cross clamping. After spinal ischemia, neurologic scores were assessed after 1, 2, 3 hours. After 3 hours rats were euthenized and spinal cords were removed for the assay of NMDAR and mGlu1 mRNA. RESULTS: The neurol ogic scores of K-2 and N groups were significantly lower than C group and K-1 group. There were no significant difference between K-1 group and C group. The NMDAR and mGlu1 gene expression was increase in C and K-1 group compared to sham operation. In K-2 and N groups, the gene expressions were significantly lesser than C group. CONCLUSIONS: The NMDAR and mGlu1 gene expressions were increased in transient spinal ischemia. Intrathecal ketamine and NBQX were effective in preventing neurologic injury after transient spinal ischemia. The NMDA antagonistic action of ketamine might involve to prevent neurologic injury.

Neuroprotective Effects of MK-801 (Dizocilpine) on Bilirubin Neurotoxicity in Mouse Cortical Cell Culture / 대한주산의학회잡지

OBJECTIVE: To evaluate whether MK-801, N-methyl-D-aspartate (NMDA) receptor antagonist, could protect against bilirubin neurotoxicity in mouse neuronal cells. METHODS: Mouse cerebral cortical cells were obtained from 14 day-old mouse fetal cerebral cortex primary culture. Cerebral cortical cells were exposed to medium containing concentrations of bilirubin 100 microM and additionally treated with 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohept-5,10-imine (MK-801, dizocilpine), 1,2,3,4-tetrahydroxy-6-nitro-2,3-dioxo-benzo [f] quinoxaline-7-sulfonamide disodium (NBQX), NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) for 4 hours. Then, the bilirubin cytotoxicity for cerebral cortical cells was quantitated by the activity of LDH released from cerebral cortical cells into the culture media. Cortical cells were stained with propidium iodide and visualized by confocal laser scanning microscopy for detection of apoptotic cells. RESULTS: After exposure for 4 hours, the cytotoxicity for cortical cells was the least in bilirubin treated with MK-801 compared to bilirubin alone, bilirubin treated with NBQX, and L-NAME (32+/-9%, 55+/-7%, 52+/-8%, 53+/-9%, respectively, p<0.05). Cells treated with MK-801 had fewer apoptotic nuclei evident on confocal microscopy. CONCLUSION: Our study suggests bilirubin neurotoxicity is mediated NMDA receptors and MK-801 is capable to prevent bilirubin-induced neuronal damage.