Serotonergic Transmission in the Hippocampus Is Subject to Multifaceted Modulation by Other Neurotransmitters.

Authors

Jae Heon Kim, Miho Song, Chan Young Lee, Yun Seob Song

Published in

International neurourology journal. Volume 30. Issue 3. Pages 214-223. Epub Sep 30, 2026.

Abstract

Serotonin (5-HT) release in the hippocampus is modulated by N-methyl-D-aspartate (NMDA) receptor activity, particularly under hypoxic conditions, but the roles of other neurotransmitter systems remain unclear. This study examined how several neurotransmitters affect spontaneous 5-HT release in rat hippocampal slices and whether these effects are direct or interneuron-mediated.
Rat hippocampal slices (400 μm) were preloaded with [3H]5-HT and superfused with oxygenated buffer. Acetylcholine (ACh), norepinephrine (NE), dopamine (DA), NMDA, γ-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.
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%-37% above baseline, P<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<0.05), but this effect was completely abolished by TTX, indicating reliance on interneuronal activity.
Hippocampal 5-HT release is differentially regulated by neurotransmitter systems: NE and DA act directly at serotonergic terminals, whereas NMDA's effect requires interneuronal activity. These findings highlight complex neurochemical interactions that may underlie serotonergic modulation in neuropsychiatric disorders.

PMID:
42839798
Bibliographic data and abstract were imported from PubMed on 07 Oct 2026.

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