Brain research
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Dextrorphan, but not dextromethorphan, exerts weak antidystonic effects in mutant dystonic hamsters.
The effects of dextromethorphan and its metabolite dextrorphan on severity of dystonia were examined in mutant dystonic hamsters, an animal model of idiopathic paroxysmal dystonia, in which recent examinations have shown antidystonic effects of selective N-methyl-D-aspartate (NMDA) receptor antagonists. Dextromethorphan and dextrorphan are non-competitive NMDA receptor antagonists which additionally exhibit affinity for sigma receptors. Dextrorphan (20 and 40 mg/kg i.p.) significantly retarded the progression of dystonia at the higher dose, whereas dextromethorphan (20, 40, 60 mg/kg i.p.) failed to exert any antidystonic effects even at high doses which caused severe effects. The lack of antidystonic efficacy of dextromethorphan may be related to its higher affinity to sigma receptors compared with dextrorphan.
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The capacity to sense changes in the concentrations of extracellular ions is an important function in several cell types. For example, hormone secretion by parathyroid cells and thyroid C-cells is primarily regulated by the level of extracellular ionized calcium (Ca2+). ⋯ Particularly high numbers of CaR expressing cells were found in regions associated with the regulation of fluid and mineral homeostasis, most notably the subfornical organ. These data suggest that the capacity to detect changes in extracellular Ca2+ concentrations may have important functional consequences in several neural systems.
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Few clinical or experimental studies have carried out systematic investigations of cutaneous and deep sensibility in areas with referred muscle pain. Therefore, no clear signs of increased or decreased psychophysical responses to various somatosensory stimuli are found in referred pain areas. In the present study, a total of 7.1 ml 5% hypertonic saline was infused over 900 s into the m. tibialis anterior of 11 subjects. ⋯ After the period with referred pain, a considerably decreased response to single and repeated, electrical stimuli (P < 0.05) was present together with significantly increased responses to contact heat stimuli at 40 degrees C and radiant heat stimuli at 75% of PT intensity (P < 0.05). The present results suggest that ongoing muscle pain can cause modality-specific (and bi-directional) sensory changes in the referred pain area. This could explain why previous studies have reported both decreased and increased responses in referred pain areas.
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The purpose of this study was to determine the effect of augmenting NMDA receptor activation on cognitive deficits produced by traumatic brain injury (TBI). Specifically, D-cycloserine (DCS), a partial agonist of the NMDA-associated glycine site, was tested as a potential cognitive enhancer. Rats were injured using lateral fluid percussion TBI (2.8 +/- .10 atm). ⋯ In contrast, the 10 mg/kg dose of DCS was ineffective in reducing injury-induced memory deficits. DCS (30 mg/kg) also significantly improved the spatial memory of sham-injured animals when compared with sham-injured animals treated with vehicle (P < 0.05). In conclusion, chronic, post-injury enhancement of the NMDA receptor is an effective strategy for ameliorating TBI-associated cognitive deficits.
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The N-methyl-D-aspartate (NMDA)-type glutamate receptors in the shell region of the nucleus accumbens (ACB) have been implicated in the modulation of dopamine release and in amphetamine-induced neurotoxicity. We used electron microscopic immunocyto-chemistry to determine the anatomical sites for NMDA-mediated effects of glutamate and for their potential interactions with dopaminergic afferents identified by the presence of tyrosine hydroxylase (TH) in this region of the rat brain. Immunogold and immunoperoxidase methods were used to localize antisera against the R1 subunit of the NMDA receptor (NMDAR1) alone or combined with TH. ⋯ The TH-immunoreactive terminals were more often seen apposed to NMDA-immunoreactive astrocytic processes and dendrites. These results provide the first ultrastructural evidence for presynaptic modulation of dopamine release by NMDA receptors in the shell of the nucleus accumbens. They also indicate that NMDA receptors modulate postsynaptic neurons receiving input from the dopaminergic afferents and suggest a previously unsuspected functional association involving glial NMDA receptors and dopaminergic afferents in this brain region.