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.