The cholinesterase inhibitor donepezil has antidepressant-like properties in the mouse forced swim test.

In FST1, immobile (while qualitatively being mildly u-shaped) and climbing behavior were not significantly modulated by donepezil but swimming showed a strong trend (one-way ANOVA: F(3, 28) = 2.92; p = 0.052), driven by the medium dose trending toward an antidepressant-like effect relative to vehicle (adjusted p = 0.081).

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In FST2, 7 days later, swimming behavior showed a trend toward modulation by donepezil dose (one-way ANOVA: F(3, 28) = 2.91; p = 0.052), driven by a mild increase in swimming (relative to vehicle) for the low and medium doses, but a decrease at the high dose (and an inverted u-shaped dose-response curve with our shuffling test; see Table S2 ).

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