Studies in which the involvement of 5-HT4 heteroreceptors in modulation of ACh release has been investigated Effects of 5-HT receptor agonists, 5-HT-releasing compounds, or 5-HT uptake inhibitors on ACh release in various brain regions and species are shown.
| Species | Brain Region | Receptor Subtypea | Drugs | Release-Modifying Concentration | Comment | References |
|---|---|---|---|---|---|---|
| Rat (CD ♀) | Frontal neocortex | 5-HT4 | BIMU 1 | 40 nmol i.c.v.: increase | Release of ACh determined by microdialysis in freely moving rats; GR 125487 (20 nmol) or GR 113808 (15 nmol) i.c.v. prevented BIMU 1 facilitation of ACh release | Consolo et al. (1994a) |
| BIMU 8 | 30–60 nmol i.c.v.: increase | |||||
| Rat (Wistar ♂) | Frontal neocortex | 5-HT4 | PCA | 1–3 mg/kg i.p.: increase | Release of ACh determined by microdialysis in freely moving rats; PCA-induced increase in ACh release inhibited by RS23597 (5 × 10–5 M) or GR 113803 (10–6 M); WAY 100135, (–)-pindolol, (–)-propranolol, ritanserin, or ondansetron had no effect | Yamaguchi et al. (1997a) |
| Rat (Wistar ♂) | Frontal neocortex | 5-HT4 | Indeloxazine | 10–5-3 × 10–5 M | Release of ACh determined by microdialysis in freely moving rats; indeloxazine applied locally by reverse dialysis increased ACh release, which was inhibited by RS23597 (5 × 10–5 M), GR 113803 (10–6 M); WAY 100135, (–)-pindolol, (–)-propranolol, ritanserin, or ondansetron had no effect | Yamaguchi et al. (1997b) |
| Guinea pig | Neocortex | 5-HT4 | BIMU 8 | 0.2–5 × 10–6 M increase | Electrically stimulated (0.5 Hz) release of 3H]ACh from slices preincubated with [3H]choline; slices were superfused in the presence of 10 μM hemicholinium-3; GR 125487 prevented effect of BIMU 8; hippocampal synaptosomes were depolarized with K+ (20 mM) | Siniscalchi et al. (1999) |
| Hippocampus | BIMU 8 | 0.2–5 × 10–6 M: no effect |
PCA, p-chloramphetamine (5-HT-releasing drug); indeloxazine, indeloxazine hydrochloride (5-HT and NE uptake inhibitor)
↵ a Receptor type involved, as suggested by the authors