Serotonin (5-HT) enhances hippocampal noradrenaline (NA) release: Evidence for facilitatory 5-HT receptors within the CNS

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Abstract
Slices of rabbit hippocampus were preincubated with 3H-noradrenaline (3H-NA), then superfused continuously in the presence of the noradrenaline (NA) uptake inhibitor (+)oxaprotilin and twice stimulated electrically. The stimulation induced tritium overflow was increased by the 5-HT receptor agonists, 5-HT, 2-methyl-5-HT and 5-carboxamidotryptamine in a concentration dependent manner; a tyramine-like displacement of NA by the 5-HT agonists was prevented by (+)oxaprotilin. The 5-HT M-receptor antagonists, MDL 72222 and ICS 205-930, inhibited the facilitatory effects of 5-HT agonists as well as the enhanced tritium overflow due to the selective 5-HT uptake inhibitor, 6-nitroquipazine: in each case, concentrations much higher than those required to block M-receptors of the periphery were necessary. At high concentrations MDL 72222, in contrast to ICS 205-930, seems to have α-adrenoceptor antagonistic activity. The 5-HT2 receptor antagonist, ketanserin, had no effect on 5-HT-induced facilitation of transmitter release; metitepin facilitated stimulationevoked transmitter release per se both in the absence and presence of phentolamine. From our results we conclude that, as on peripheral nerve endings, also on central noradrenergic terminals, facilitatory 5-HT receptors are present that modulate NA release. The enhanced tritium overflow following 6-nitroquipazine may be due to an increased release of endogenous 5-HT, a suggestion which supports the hypothesis of a physiological innervation of these facilitatory 5-HT receptors on NA terminals.