FIGURE 2.

Specificity of 5HT_2A-R on Aβ regulation. (a) ISF Aβ₄₀ was measured by in vivo microdialysis following administration of M100907 (i.p.) every 12 hr at 0.1 mg/kg, 0.3 mg/kg, 1.0 mg/kg, and then 3.0 mg/kg. Aβ declined by 18.6 ± 3.9% (p = .063), 31.6 ± 4.7% (p = .0185), 46.2 ± 3.9% (p < .0001), and 56.6 ± 7.1% (p < .0001), respectively, at each of the doses compared to vehicle-treated mice at the during the same time period (n = 6–10 per group). (b) ISF Aβ₄₀ was assessed after administration of SB206553, a selective 5HT_2B/C-R inverse agonist (1 μM) or SB242084, a selective 5HT_2C-R antagonist (50 nM) by reverse microdialysis. Neither compound reduced ISF Aβ levels over a 14-hr period (n = 5–6 mice per group). (c) Murine Aβ in the ISF was measured in 3-month-old C57Bl/6 wildtype mice or 5HT_2A-R knockout mice following administration of 1 mg/kg Pimavanserin (s.c.). Pim (1 mg/kg) reduced ISF Aβ₄₀ significantly in wildtype mice by 51.1 ± 5.8% (p = .0002), but had no effect in 5HT_2A-R knockout mice (n = 4–6 mice per group). Data present as mean ± SEM