Serotonin (5-HT) enhances hippocampal noradrenaline (NA) release: evidence for facilitatory 5-HT receptors within the CNS.
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 alpha-adrenoceptor antagonistic activity. The 5-HT2 receptor antagonist, ketanserin, had no effect on 5-HT-induced facilitation of transmitter release; metitepin facilitated stimulation-evoked 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.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008376:Maprotiline / Q000031:analogs & derivatives / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology; D000077526:Tropisetron
D007211:Indoles; D011985:Receptors, Serotonin; D014326:Tropanes; D008376:Maprotiline; D012701:Serotonin; C027299:hydroxymaprotilin; D000077526:Tropisetron; C042253:bemesetron; D009638:Norepinephrine