Fig. 1
From: Redundant Gs-coupled serotonin receptors regulate amyloid-β metabolism in vivo
A small subset of 5-HT receptors reduce ISF Aβ levels in vivo. Selective agonists for individual 5-HT receptors or vehicle (DMSO) were infused via reverse microdialysis (rev md) in 2–3 month old APP/PS1 hemizygous mice. a As assessed by microdialysis, broad activation of 5-HTRs by serotonin (2 mM by rev md) directly or by citalopram (10 mg/kg i.p.), a SSRI, caused a decrease in ISF Aβ levels. Similarly, reverse microdialysis treatment with agonists for 5-HT4R (ML10302, 400 nM), 5-HT6R (ST1936, 1.3 μM), and 5-HT7R (AS19, 83 nM) induced a reduction in ISF Aβ in living mice. b After hours 22-24 of continuous treatment, ML10302, ST1936, and AS19 reduced ISF Aβx-40 by 25.2 ± 3.4 % (p < 0.01; n = 6), by 24.8 ± 6.1 % (p < 0.01; n = 6), and by 22.5 ± 5.5 % (p < 0.05; n = 6), respectively. Serotonin and citalopram also significantly reduced ISF Aβ by 26.5 ± 5.4 % (p < 0.01; n = 7) and 25.5 ± 3.4 % (p < 0.05; n = 5), respectively. c Agonist treatment for 5-HT1AR (Ipsapirone, 1 μM) or 5-HT2CR (WAY161503, 400 nM) showed no significant reduction of ISF Aβ. d After 24 h of continuous treatment, Ipsapirone reduced ISF Aβx-40 to 91.2 ± 9.4 % (n = 6) and WAY161503 increased ISF Aβx-40 to 119.9 ± 8.6 % (n = 8). e Citalopram (10 mg/kg, i.p.) administered to young C57Bl6 wildtype mice significantly reduced ISF Aβ levels by 32 ± 4.2 % at 21–24 h after treatment compared to vehicle-treated (PBS) mice (p < 0.001; n = 6). f Mice were treated with selective 5-HT7R antagonist SB258719 (3.16 μM) for 8 h followed by co-administration of 5-HT7R agonist, AS19, (83nM) for 24 h by reverse microdialysis (n = 4). The antagonist completely blocked the effect of the agonist. The antagonist alone had no significant effect on ISF Aβ levels. Data presented as mean ± SEM. Asterisks mark p-values < 0.05; double asterisks mark p-values < 0.01; triple asterisks mark p-values 0.001