Release of 5-hydroxytryptamine (5-HT) from medullary and mesencephalic raphé neurones after grafting to the rat hippocampus: evidence for regulation by 5-HT1A autoreceptors.
The overflow and metabolism of serotonin (5-HT) from transplants of embryonic medullary and mesencephalic raphé neurones in the previously 5-HT-denervated hippocampus have been analyzed in vivo using microdialysis. Output of 5-HT and its metabolite 5-hydroxyindolacetic acid (5-HIAA) from such grafts was as great (medullary) or greater (mesencephalic) than that measured in the normal intact hippocampus. Systemic administration of the putative 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) led to a 50-80% reduction in 5-HT levels in hippocampal dialysates from both intact and raphé grafted hippocampus. Since 8-OH-DPAT normally reduces 5-HT release from the nerve terminal via activation at the somatodendritic 5-HT1A autoreceptor and subsequent inhibition of impulse flow, the results indicate that 5-HT output from both medullary and mesencephalic raphé grafts can be regulated by autoreceptors and is dependent on serotoninergic neuronal activity.
Sharp
T
T
MRC Clinical Pharmacology Unit, Radcliffe Infirmary, Oxford, U.K.
Foster
G A
GA
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D016380:Brain Tissue Transplantation; D016332:Fetal Tissue Transplantation; D006624:Hippocampus / Q000502:physiology*; D008526:Medulla Oblongata / Q000166:cytology / Q000378:metabolism*; D008636:Mesencephalon; D009474:Neurons / Q000378:metabolism / Q000637:transplantation*; D011903:Raphe Nuclei / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin