Neuroscience letters
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Neuroscience letters · Oct 1991
Novel substance P antagonist, CP-96,345, blocks responses of cat spinal dorsal horn neurons to noxious cutaneous stimulation and to substance P.
Responses of dorsal horn neurons to iontophoretic application of substance P (80-120 nA), and to noxious thermal and noxious mechanical stimulations of the receptive field in the hind limb were tested in adult cats before and after the administration of the specific, non-peptide, NK-1 receptor antagonist CP-96,345 (0.5 mg/kg, i.v.). CP-96,345 inhibited the response of the neurones to substance P and also the response of these substance P-sensitive neurones to noxious thermal stimulation. ⋯ The effect of CP-96,345 on the response of neurones to noxious mechanical stimulation was variable. The results confirm the role of substance P in thermal nociception.
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Neuroscience letters · Sep 1991
Effects of NMDA and calcium channel antagonists on regional cerebral blood flow.
N-Methyl-D-aspartate (NMDA) antagonists and voltage-dependent calcium channel antagonists were tested to determine potential effects on regional cerebral blood flow in the normal rabbit brain. Ketamine had no effects on cortical or hippocampal blood flow, but was found to significantly decrease blood flow in the inferior colliculus. ⋯ Dextromethorphan and dextrorphan, which have been shown to act at the NMDA receptor as well as the dihydropyridine calcium channel, decreased blood flow in the inferior colliculus, but showed no effects in the cortex or hippocampus. These results suggest that the neuroprotective NMDA antagonists do not increase blood flow primarily in the normal brain.
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Neuroscience letters · Sep 1991
Neuroma formation and numbers of axons in a rat model of experimental peripheral neuropathy.
Two weeks following chronic partial constriction of rat sciatic nerve, the perineurium was disrupted and a neuroma had formed at the constriction site in all nerves (n = 5). Axon counts demonstrated an 84-99% and a 62-84% decrease in myelinated and unmyelinated axons respectively, distal to the lesion. ⋯ There was considerable disparity in fiber loss from animal to animal, but similar behavioral changes were demonstrated by all animals. These results are discussed with reference to previously published data and possible mechanisms underlying the behavioral manifestations of this neuropathy model.
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Neuroscience letters · Sep 1991
Inverse but not full benzodiazepine agonists modulate recombinant alpha 6 beta 2 gamma 2 GABAA receptors in transfected human embryonic kidney cells.
We compared the modulation of GABA (gamma-aminobutyric acid)-activated currents by benzodiazepines in recombinant GABAA receptors containing either one of two alpha subunits, alpha 1 or alpha 6. Lüddens et al. (Nature, 346 (1990) 648-651) have previously demonstrated that the alpha 6 subunit is part of a cerebellar receptor subtype which selectively binds Ro15-4513, an antagonist of alcohol-induced motor ataxia. ⋯ In contrast, flunitrazepam (FNZM), a benzodiazepine agonist, increases GABA-activated currents in alpha 1 beta 2 gamma 2 receptors, but not in alpha 6 beta 2 gamma 2 receptors. This study lends further support to the hypothesis that the binding sites of full and partial inverse agonists are different.
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Neuroscience letters · Jul 1991
The effects of pentobarbital and benzodiazepines on GABA-responses in the periphery and spinal cord in vitro.
Pentobarbital and benzodiazepines were compared in their interaction with the gamma-aminobutyric acid (GABA) antagonists picrotoxin and bicuculline on GABAA receptor-mediated events. On excised vagal nerves and dorsal roots pentobarbital, in contrast to the benzodiazepines diazepam, lorazepam and flurazepam, was able to enhance GABA-induced depolarizations recorded in the presence of picrotoxin or bicuculline. ⋯ Pentobarbital overcame the effects of picrotoxin, whereas diazepam and midazolam were without effect. These results may be explained by the suggestion that the GABA receptors in these test systems are not tightly associated with the benzodiazepine receptor activated by diazepam, lorazepam, midazolam and flurazepam, and correspond to the recently described GABAA2 subdivision of GABA receptors.