Neuroscience
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Comparative Study
Ultra-low dose naltrexone potentiates the anticonvulsant effect of low dose morphine on clonic seizures.
Significant potentiation of analgesic effects of opioids can be achieved through selective blockade of their stimulatory effects on intracellular signaling pathways by ultra-low doses of opioid receptor antagonists. However, the generality and specificity of this interaction is not well understood. The bimodal modulation of pentylenetetrazole-induced seizure threshold by opioids provide a model to assess the potential usefulness of this approach in seizure disorders and to examine the differential mechanisms involved in opioid anti- (morphine at 0.5-3 mg/kg) versus pro-convulsant (20-100 mg/kg) effects. ⋯ However, ultra-low dose naltrexone could not increase the maximal anticonvulsant effect of morphine (1-3 mg/kg), possibly due to a ceiling effect. The proconvulsant effects of morphine on seizure threshold were minimally altered by ultra-low doses of naltrexone while being completely blocked by a higher dose (1 mg/kg) of the antagonist. The present data suggest that ultra-low doses of opioid receptor antagonists may provide a potent strategy to modulate seizure susceptibility, especially in conjunction with very low doses of opioids.
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Leptin is a 16 kDa hormone that is produced by adipose tissue and has a central effect on food intake and energy homeostasis. The ability of leptin to cross the blood-brain and blood-cerebrospinal fluid (CSF) barriers and reach or leave the CNS was studied by the bilateral in situ brain perfusion and isolated incubated choroid plexus techniques in the rat. Brain perfusion results indicated that [(125)I]leptin reached the CNS at higher concentrations than the vascular marker, confirming that [(125)I]leptin crossed the brain barriers. ⋯ Studies using the incubated rat choroid plexus model found that [(125)I]leptin could cross the apical membrane of the choroid plexus to leave the CSF. However, this movement was not sensitive to unlabelled human leptin or specific transport inhibitors/modulators (including probenecid, digoxin, deltorphin II, progesterone and indomethacin). This study supports the concept of brain-barrier regulation of leptin distribution to the CNS, and highlights an important link between leptin and the cerebellum.
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Polyimide regenerative electrodes (RE) constitute a promising neural interface to selectively stimulate regenerating fibers in injured nerves. The characteristics of the regeneration through an implanted RE, however, are only beginning to be established. It was recently shown that the number of myelinated fibers distal to the implant reached control values 7 months postimplant; however, the functional recovery remained substantially below normal [J Biomed Mater Res 60 (2002) 517]. ⋯ Moreover, smaller ganglion cells regenerated better than large neurons by a significant 13.8%. These results indicate that the RE is not an obstacle for the re-growth of sensory fibers, but partially hinders fiber regeneration from motoneurons. They also suggest that fine fibers may be at an advantage over large ones to regenerate through the RE.
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Evidence has accumulated over the years supporting glutamate as the primary neurotransmitter used by hair cells in afferent cochlear neurotransmission. Besides acting on ionotropic glutamate receptors, glutamate also activates second messenger systems via G-protein-coupled metabotropic glutamate receptors (mGluRs) to modulate neuronal excitability. However, it is unclear whether mGluRs participate in cochlear neurotransmission. ⋯ In contrast, blocking mGluRIs lowered the amplitude of compound action potentials at louder sound levels and reduced the noise-induced temporary threshold shift. Our results suggest that although mGluRIs did not initiate fast excitatory cochlear neurotransmission, their activation contributed to the growth of excitatory responses of the cochlea. As a result, the cochlea was more resistant to noise-induced temporary hearing losses without the activation of mGluRIs in SG neurons.
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Recent in vivo electrophysiological studies suggest that chronic dopamine depletion alters profoundly the firing pattern of basal ganglia neurons. These changes may disrupt the processing of cortical information flow from the striatum to the output nuclei, and presumably underlie the clinical manifestations of Parkinson's disease. We have recently reported that chronic nigrostriatal lesions induce changes in the functional state of striatal medium-spiny neurons (MSNs) that could facilitate spreading of cortical synchronous activity (approximately 1 Hz) to striatal target nuclei. ⋯ Following systemic administration of SKF38393 or SKF81279 the membrane potential of striatal MSNs was upheld into a more hyperpolarized value and action potential firing probability decreased. D1 agonists also increased the latency to the cortically driven plateau depolarization and reduced the peak potential of the short latency depolarizing postsynaptic response to a more hyperpolarized value. The present study provides in vivo evidence indicating that pharmacological stimulation of D1-class dopamine receptors can modulate the flow of cortical information through the striatum in the parkinsonian state.