Neuroscience
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To investigate the mechanism of vincristine-induced pain in humans undergoing chemotherapy we have established a model of vincristine-induced hyperalgesia in rat. Vincristine (100 micrograms/kg) was administered daily over a period of two weeks. An acute dose-dependent decrease in mechanical nociceptive threshold and an increased response to non-noxious mechanical stimuli ("hyperalgesia") occurred after the second day of administration. ⋯ At a dose that produced hyperalgesia (100 micrograms/kg), vincristine did not cause a significant motor deficit. Peripheral administration of a mu-opioid agonist did not reduce vincristine-induced acute hyperalgesia. Hyperalgesia induced by vincristine in the rat provides a good model for the experimental study of painful peripheral neuropathies in human patients receiving vincristine as a chemotherapeutic agent.
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The regional distribution of the serotonin uptake system was studied in rat brain using a specific polyclonal antibody raised against the putative extracellular loop between transmembrane domains 7 and 8 of the cloned rat serotonin transporter. Light microscope analysis with fluorescence and avidin-biotin-peroxidase techniques revealed a punctate staining as well as numerous labelled thin fibres, which exhibited accumulation of reaction end-product deposit over varicosities. These immunopositive processes were widely and heterogeneously distributed in the rat brain. ⋯ In addition, some immunoreactive fibres were present in the molecular and granular layers of the cerebellum as well as in the cochlear and olivary nuclei. In none of the regions analysed was evidence for glial staining obtained. The present immunocytochemical data reveal a widespread and heterogeneous distribution of the serotonin transporter in rat brain and suggest that serotoni transporter is preferentially sorted into axons, where it appears concentrated at varicosities and terminal boutons.