Raphé grafts and 3,4-diaminopyridine-evoked overflow of serotonin in the rat hippocampus after 5,7-dihydroxytryptamine lesions: evidence for 5-HT1A autoreceptors.
A first experiment verified that the overflow of 5-HT evoked by 75 microM 3,4-diaminopyridine in superfused hippocampal slices was calcium-dependent, tetrodotoxin-sensitive and modulable by drugs acting on 5-HT autoreceptors. Subsequently, the technique was used in rats to investigate the effects of 5,7-dihydroxytryptamine lesions and intrahippocampal serotonergic grafts. The lesions reduced the accumulation (-81%) and relative evoked overflow (-23%; absolute evoked overflow -86%) of [ H]5-HT, but increased the relative baseline overflow (+23%; absolute baseline overflow -78%). Grafts partially compensated for these effects. In slices from grafted rats, the evoked overflow was reduced by application of a 5-HT receptor agonist (8-OH-DPAT), a response not found in sham-operated and lesion-only rats. Although the graft-induced effects were less marked than in previous studies, they were beneficial and modulated by a mechanism that normally does not operate in the intact hippocampus.
Schweizer
Theresa
T
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Universität Freiburg, Neuropharmakologisches Labor, Hansastrasse 9A, D-79104 Freiburg, Germany.
Birthelmer
Anja
A
Jeltsch
Hélène
H
Cassel
Jean-Christophe
JC
Jackisch
Rolf
R
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015116:5,7-Dihydroxytryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000077770:Amifampridine; D000818:Animals; D017660:Autoreceptors / Q000187:drug effects / Q000378:metabolism*; D016380:Brain Tissue Transplantation / Q000379:methods; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003714:Denervation; D005333:Fetus; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000637:transplantation*; D009498:Neurotoxins / Q000494:pharmacology; D009924:Organ Culture Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism / Q000601:surgery*; D051381:Rats; D020318:Rats, Long-Evans; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D017660:Autoreceptors; D009498:Neurotoxins; D026902:Potassium Channel Blockers; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D013779:Tetrodotoxin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D015761:4-Aminopyridine; D000077770:Amifampridine; D002118:Calcium