Serotonin release in the rat brain cortex is inhibited by neuropeptide Y but not affected by ACTH1-24, angiotensin II, bradykinin and delta-sleep-inducing peptide.
Schlicker. E E; Gross. G G; Fink. K K; Glaser. T T; Göthert. M M
Key Findings
- NPY, PYY, and pancreatic polypeptide inhibit electrically evoked serotonin release in rat cortex slices.
- The inhibition by NPY is strongest at low stimulation frequencies (1 Hz) and weaker at higher frequencies (10 Hz).
- NPY also reduces calcium‑triggered serotonin release and lowers forskolin‑stimulated cAMP accumulation, suggesting a presynaptic receptor mechanism.
Practical Outcomes
- For biohackers, this study suggests that boosting NPY activity could dampen serotonin signaling, which might influence mood, appetite, or stress responses. However, the work is done in isolated rat brain tissue, so there are no human dosage guidelines or proven benefits yet. Until more translational data are available, it’s mainly a mechanistic insight rather than a ready‑to‑use protocol.
Summary
In rat brain slices, the peptide neuropeptide Y (NPY) and related gut hormones (PYY and pancreatic polypeptide) were found to block the release of serotonin, while other tested peptides had no effect. The block was strongest at low stimulation frequencies and involved presynaptic receptors that also lowered a signaling molecule called cAMP.
Abstract
The effects of neuropeptide Y (NPY), peptide YY (PYY), pancreatic polypeptide and of another four peptides on the electrically evoked 3H overflow were studied in superfused rat brain cortex slices preincubated with 3H-serotonin. In addition, we determined the effect of NPY on the Ca2(+)-induced 3H overflow from rat brain cortex slices and synaptosomes (preincubated with 3H-serotonin) and on the forskolin-stimulated accumulation of cAMP in a membrane fraction from rat brain cortex. The electrically (3 Hz) evoked 3H overflow was inhibited by PYY, NPY and pancreatic polypeptide (decreasing order of potency), but not affected by ACTH1-24, angiotensin II, bradykinin and delta-sleep-inducing peptide. The inhibitory effect of NPY did not change when the stimulation frequency was lowered to 1 Hz, but was markedly reduced at 10 Hz. The inhibitory effect of a presumably maximally active concentration of PYY was not altered in the presence of NPY or pancreatic polypeptide (effects not additive), whereas the inhibition produced by a maximally active concentration of the alpha 2-adrenoceptor agonist clonidine was further increased by NPY. NPY also inhibited (1) the tritium overflow, evoked by introduction of Ca2+, in slices superfused with Ca2(+)-free and K(+)-rich medium containing tetrodotoxin, (2) the tritium overflow, evoked by simultaneously increasing Ca2+ and K+ in the superfusion fluid of synaptosomes previously superfused with Ca2(+)-free medium and (3) the forskolin-stimulated accumulation of cAMP in rat brain cortex membranes. The present results suggest that NPY inhibits serotonin release in the rat brain via presynaptic NPY receptors, which are also activated by PYY and pancreatic polypeptide and may be negatively coupled to an adenylate cyclase.
Study Information
pubmed
1991
10.1007/bf00168597