Fig. 5: Donepezil augments fear extinction in a mouse model of PTSD-like behavior.

A Schematics diagram of the SPS model used for contextual conditioning and extinction paradigm. Freezing time to context after induction of fear in WT mice was measured for 9 consecutive days in extinction-learning trials whereby the animals were re-exposed to the context for 3 min/day without receiving the foot shock. B Donepezil treatment during the extinction trials reduces freezing behavior in the SPS model. WT mice were treated each day with donepezil starting at day 8 after measuring the fear response and each following day immediately after each extinction trial. Note the overall higher freezing time in saline-treated stressed group. In contrast, donepezil-treated SPS group mice could extinguish their fear from the 5th extinction trial onwards similarly to the non-stressed animals. *p < 0.05, n = 18–22/group, statistical analysis by two-way ANOVA followed by Tukey’s post-hoc multiple comparison test. C Treatment of animals with the GABA agonist midazolam does not affect fear extinction relative to the SPS saline group (n = 8–12/group). Note that neither donepezil nor midazolam affects extinction learning in condition of non-stress (Control Donepezil in B and Control Midazolam in C relative to Control Saline).