Neuroscience
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The N-methyl-D-aspartate-evoked release of [3H]acetylcholine previously formed from [3H]choline was estimated in striosome- (identified by [3H]naloxone binding) or matrix-enriched areas of the rat striatum using an in vitro microsuperfusion procedure. Experiments were performed in either the absence or the presence of dopaminergic and/or GABAergic receptor antagonists. Although the cell bodies of the cholinergic interneurons were mainly found in the matrix, in the absence of magnesium, N-methyl-D-aspartate (50 microM) stimulated the release of [3H]acetylcholine in both striatal compartments. ⋯ Indicating that released GABA facilitates N-methyl-D-aspartate responses, the blockade of GABAA receptors with bicuculline (5 microM) reduced the 50 microM N-methyl-D-aspartate-evoked release of [3H]acetylcholine in both striatal compartments and the 1 mM N-methyl-D-aspartate+D-serine response in the matrix. These effects result from an inhibition by GABA of the evoked release of dopamine, since the reducing effects of bicuculline on N-methyl-D-aspartate responses were not observed under the complete blockade of dopaminergic transmission by the D1 and D2 receptor antagonists. Further demonstrating a facilitatory role of GABA in the control of N-methyl-D-aspartate-evoked release of [3H]acetylcholine, in the presence of bicuculline, (-)-sulpiride and SCH23390 alone or in combination enhanced, in both compartments, the responses induced not only by 1 mM N-methyl-D-aspartate+D-serine, but also by 50 microM N-methyl-D-aspartate.
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The protein Fos is a transcription factor which is quickly induced in response to a variety of extracellular signals. Since this protein is expressed in a variety of neuronal systems in response to activation of synaptic afferents, it has been suggested that it might contribute to activity-dependent plasticity in neural networks. The present study investigated the effect of cortical electrical stimulation on the expression of Fos in the basal ganglia in the rat, a group of structures that participate in sensorimotor learning. ⋯ In the subthalamic nucleus, Fos expression evoked by cortical stimulation is also confined to discrete regions of the nucleus, the localizations corresponding to the primary projection site of the stimulated cortical cells. These results indicate that in addition to its phasic synaptic influence on the basal ganglia, the cerebral cortex could exert a long-term effect on the functional state of this system via a genomic control. Since the basal ganglia are involved in sensorimotor learning and motor habit formation, it is tempting to speculate that the activity-dependent Fos induction at corticostriatal and subthalamic synapses may contribute to consolidate the functionality of the neuronal networks activated during the completion of given motor tasks.
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Tight ligation of the fifth and sixth lumbar segmental nerves in the rat provides a model of neuropathic pain. We used this model to assess the changes in primary afferent input to the dorsal horn in neuropathic pain syndromes. Dorsal roots and ganglia were examined for up to 32 weeks following segmental nerve ligation. ⋯ These findings indicate that although there is a great loss of dorsal root ganglion cells, there is dramatic sprouting of myelinated fibres and possibly some sprouting of unmyelinated fibres in the dorsal roots. Additionally, a difference in the responses of unmyelinated and myelinated fibres to this peripheral nerve injury is revealed. These changes in dorsal root ganglion cells and their central axons may underlie certain aspects of abnormal pain syndromes because of changes in the types and quantity of input the dorsal horn receives.
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The expression of the transcription factor c-JUN was investigated in the rat fascia dentata under normal conditions and after entorhinal cortex lesion. As shown by immunocytochemistry and in situ hybridization histochemistry c-JUN and its messenger RNA are present in the principal cell layers of the dentate gyrus and Ammon's horn (except hippocampal region CA2). Pre-embedding immunogold electron microscopy revealed an almost exclusive nuclear localization of c-JUN, where it is associated with chromatin. ⋯ These results point to a specific role of c-JUN in the granule cells of the fascia dentata in the normal animal and in rats with entorhinal cortex lesions. The selective induction of c-JUN after entorhinal lesion could be one of the first molecular steps that regulate transneuronal changes within granule cells after their denervation. A different mechanism has to be assumed for GABAergic interneurons known to receive an entorhinal innervation as well.
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Nociceptin (a heptadecapeptide also known as orphanin FQ) is a potent endogenous agonist of the opioid receptor-like1 receptor and has a sequence similar to dynorphin A. It has been reported that intracerebroventricularly injected nociceptin produced hyperalgesia in mice and that intrathecal injection of nociceptin inhibits the spinal sensitization. In the present study, we investigated the effect of intrathecally administered nociceptin in the rat formalin test (a model of inflammatory pain) and the rat hot plate test. ⋯ These effects of nociceptin were not antagonized by the co-administration of naloxone. Intrathecal injection of nociceptin had no effect on the hot plate test. These data suggest that nociceptin plays an important role in spinal nociceptive transmission through the activation of a naloxone-insensitive receptor, and spinally administered nociceptin produces an analgesic effect during the rat formalin test, but not the hot plate test.