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Abstract

Possible reasons for why a new study could not replicate our finding that the serotonin reuptake inhibitor citalopram decreased amyloid β concentrations in the cerebrospinal fluid of healthy volunteers.

Fig. 1. Effect of SSRIs on ISF Aβ concentrations in APP/PS1 transgenic mice

(A) Young 3- to 4-month-old APP/PS1 hemizygous mice (pre-plaque) were implanted with unilateral microdialysis probes into the hippocampus [as described in (6)]. Baseline ISF Aβ concentrations were established in each mouse for 7.5 hours, and then mice were administered a single dose of either vehicle [phosphate-buffered saline (PBS)], escitalopram (5 mg/kg), or citalopram (10 mg/kg) intraperitoneally (i.p.). ISF Aβ was measured every 60 min for an additional 24 hours. The citalopram data are from a previously published study (6), and the escitalopram data are from new studies using identical methods. Using a two-way analysis of variance (ANOVA) with repeated measures and Bonferroni correction for multiple comparisons, there was a significant difference between the drug treatment groups compared to vehicle; ***P < 0.001. (B) By hours 22 to 24 after drug dosing, there was a 16.0 ± 6.4% (*P = 0.03, n = 6) and a 26.0 ± 5.4% (*P = 0.0013, n = 4) decrease in ISF Aβ with escitalopram and citalopram, respectively, compared to vehicle-treated mice (n = 6) (one-way ANOVA compared to vehicle; mean ± SEM). ns, not significant.