In vivo measurement using microdialysis of the release and metabolism of 5-hydroxytryptamine in raphe neurones grafted to the rat hippocampus.
The overflow and metabolism of serotonin (5-hydroxytryptamine; 5-HT) from transplants of embryonic medullary and mesencephalic raphe neurones in the previously 5-HT-denervated hippocampus have been analyzed in vivo using intracerebral dialysis. The average density of 5-HT-immunoreactive fibres in the grafted hippocampus was less than in nonlesioned hippocampus. Nonetheless, both basal and potassium-stimulated levels of 5-HT in the dialysates were restored to approximately normal after transplantation of medullary raphe cells, whereas mesencephalic implants resulted in over twice the 5-HT output observed in control hippocampus. However, 5-hydroxyindoleacetic acid (5-HIAA) overflow was increased only after grafting of mesencephalic raphe and then only to normal levels; medullary implants, by contrast, failed to enhance 5-HIAA output above that from lesion-only hippocampus. The evidence of a relative hyperactivity of the grafted neurones may explain the disproportionate improvements in various lesion-induced behavioural deficits after grafting of nervous tissue. In addition, differences in the presynaptic regulation of 5-HT release and metabolism are also apparent in the transplants; these variations are dependent on the precise origin of the serotoninergic cells.
Sharp
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T
MRC Clinical Pharmacology Unit, Radcliffe Infirmary, Oxford, England.
Foster
G A
GA
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D003714:Denervation; D003956:Dialysis / Q000379:methods; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D009474:Neurons / Q000378:metabolism / Q000637:transplantation*; D011903:Raphe Nuclei / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid