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This study examined how several neurotransmitters affect spontaneous 5-HT release in rat hippocampal slices and whether these effects are direct or interneuron-mediated.Methods: Rat hippocampal slices (400 \u03bcm) were preloaded with [3H]5-HT and superfused with oxygenated buffer. Acetylcholine (ACh), norepinephrine (NE), dopamine (DA), NMDA, \u03b3-aminobutyric acid (GABA), glycine, or neuropeptide Y (NPY) were applied for 20 minutes, and [3H]5-HT release was measured in 10-minute fractions. Tetrodotoxin (TTX) was used in parallel experiments to block action potential-dependent neurotransmission.Results: In control slices, spontaneous [3H]5-HT release reached a stable baseline after approximately 50 minutes of superfusion. ACh (10-5M), GABA (10-5M), glycine (10-5M), and NPY (10-6M) did not significantly affect 5-HT release relative to control. In contrast, NE (10-5M) and DA (10-5M) significantly increased 5-HT release (peaking at ~15%\u201337% above baseline, P&lt;0.05), and these effects persisted in the presence of TTX, suggesting a direct action on serotonergic terminals. NMDA (10-4M) also transiently enhanced 5-HT release (~22% above baseline, P&lt;0.05), but this effect was completely abolished by TTX, indicating reliance on interneuronal activity.Conclusions: Hippocampal 5-HT release is differentially regulated by neurotransmitter systems: NE and DA act directly at serotonergic terminals, whereas NMDA\u2019s effect requires interneuronal activity. These findings highlight complex neurochemical interactions that may underlie serotonergic modulation in neuropsychiatric disorders.<\/jats:p>","DOI":"10.5213\/inj.2550346.173","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:26:12Z","timestamp":1790655972000},"page":"214-223","update-policy":"https:\/\/doi.org\/10.5213\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serotonergic Transmission in the Hippocampus Is Subject to Multifaceted Modulation by Other Neurotransmitters"],"prefix":"10.5213","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4490-3610","authenticated-orcid":true,"given":"Jae Heon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Urology, Soonchunhyang University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8345-6686","authenticated-orcid":true,"given":"Miho","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Urology, Soonchunhyang University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9559-5286","authenticated-orcid":true,"given":"Chan Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0909-3341","authenticated-orcid":true,"given":"Yun Seob","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Urology, Soonchunhyang University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3166","reference":[{"key":"ref1","volume-title":"","author":"Dingledine","year":"1984","type":"book"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(75)90817-3","type":"journal-article"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(74)90790-2","type":"journal-article"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(78)90810-7","type":"journal-article"},{"key":"ref5","first-page":"1","type":"journal-article","volume-title":"The organization of the ascending catecholamine neuron systems in the rat brain as revealed by the glyoxylic acid fluorescence method","author":"Lindvall","year":"1974"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901890406","type":"journal-article"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(77)90407-3","type":"journal-article"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(77)90106-6","type":"journal-article"},{"key":"ref9","first-page":"467","type":"journal-article","volume-title":"The central adrenergic system. 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