Fig. 4.

AChE knockdown in the hippocampus promotes anxiety-like behavior in mice. Infusion of shAChE into the hippocampus (n = 10 per group) decreased both time spent in open arms in the elevated plus maze test (A, Left) and time spent in the light compartment of the light–dark box (A, Right). AChE knockdown in the hippocampus increased depression-like behavior in mice. Infusion of shAChE into the hippocampus increased immobility time in the tail suspension (B, Left) and forced-swim (B, Right) tests, with no effects on locomotor activity (C). AChE knockdown in the hippocampus promotes stress susceptibility in mice. Ten days of social defeat stress decreased social interaction in WT mice (D). Infusion of shAChE into the hippocampus decreased social interaction after submaximal defeat stress compared with mice receiving scrambled shRNA infusion (E). Expression of hAChE in the hippocampus prevents AChE knockdown and rescues the behavioral effect of shAChE infusion in mice. Infusion of AAV-hAChE in the hippocampus prevented prodepressive effects of hippocampal shAChE delivery in the tail suspension and forced-swim tests, as well as in the submaximal social defeat paradigm. Fluoxetine reversed the behavioral effects of hippocampal shRNA-mediated AChE knockdown. Acute administration of fluoxetine (10 mg/kg) reversed the effects of AChE knockdown in the hippocampus in the tail suspension test (F, Left). Chronic administration of fluoxetine (10 mg/kg) reversed the effects of shAChE infusion in the social defeat paradigm (F, Right); n = 8–10 per group. All data are expressed as mean ± SEM. *P < 0.05; **P < 0.01, ***P < 0.001.