Neuroscience letters
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Neuroscience letters · Mar 2014
Opioid and noradrenergic contributions of tapentadol in experimental neuropathic pain.
Tapentadol is a dual action molecule with mu opioid agonist and norepinephrine (NE) reuptake blocking activity that has recently been introduced for the treatment of moderate to severe pain. The effects of intraperitoneal (i.p.) morphine (10mg/kg), tapentadol (10 or 30 mg/kg) or duloxetine (30 mg/kg), a norepinephrine/serotonin (NE/5HT) reuptake inhibitor, were evaluated in male, Sprague-Dawley rats with spinal nerve ligation (SNL) or sham surgery. Additionally, the effects of these drugs on spinal cerebrospinal fluid (CSF) NE levels were quantified. ⋯ This could be detected 30 min following tapentadol (30 mg/kg) in both sham and SNL groups. Surprisingly, while the dose of morphine studied reversed tactile hypersensitivity in nerve-injured rats, CSF NE levels were significantly reduced in both sham- and SNL rats. The data suggest that tapentadol elicits enhanced elevation in spinal NE levels in a model of experimental neuropathic pain offering a mechanistic correlate to observed clinical efficacy in this pain state.
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Neuroscience letters · Feb 2014
Neocortical integration of transplanted GABA progenitor cells from wild type and GABA(B) receptor knockout mouse donors.
Most cortical interneurons originate in a region of the embryonic subpallium called the medial ganglionic eminence (MGE). When MGE cells are transplanted into cerebral cortex, these progenitors migrate extensively and differentiate into functional inhibitory neurons. Although MGE progenitors have therapeutic potential following transplantation, it is unknown precisely how these cells distribute within neocortical lamina of the recipient brain. ⋯ MGE-derived neurons from WT and GABA(B1)R KO mice preferentially and densely distributed in neocortical layers 2/3, 5 and 6. As expected, MGE-derived neurons differentiated into parvalbumin+ and somatostatin+ interneurons within these neocortical lamina. Our findings provide insights into the anatomical integration of MGE-derived interneurons following transplantation.
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Neuroscience letters · Feb 2014
Application of intermittent galvanic vestibular stimulation reveals age-related constraints in the multisensory reweighting of posture.
In this study we examined the effects of intermittent short-duration Galvanic Vestibular Stimulation (GVS) during a multisensory perturbation of posture in young and elderly adults. Twelve young (24.91±6.44 years) and eleven elderly (74.8±6.42 years) participants stood upright under two task conditions: (a) quiet standing and (b) standing while receiving pseudo-randomly presented bipolar 2 s GVS pulses. ⋯ Intermittent GVS decreased the excessive postural sway induced by the concurrent visual and proprioceptive perturbation in young but not in elderly participants. It is suggested that GVS increases sensory reliance on the vestibular system while elderly adults are less able to exploit this stimulation in order to reduce the destabilizing effect of the multisensory perturbation on their posture.
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Using functional magnetic resonance imaging in human participants, we show that sedation by propofol to the point of lost overt responsiveness during the performance of an auditory verbal memory task unexpectedly increases functional connectivity of the precuneus with cortical regions, particularly the dorsal prefrontal and visual cortices. After recovery of consciousness, functional connectivity returns to a pattern similar to that observed during the wakeful baseline. In the context of a recent proposal that highlights the uncoupling of consciousness, connectedness, and responsiveness in general anesthesia, the increased precuneus functional connectivity under propofol sedation may reflect disconnected endogenous mentation or dreaming that continues at a reduced level of metabolic activity.