Evidence has shown that sex differences affect the symptoms and the response to treatments in neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). Extinction, as a therapeutic method, and reinstatement, as a method that facilitates shock-related memory retrieval, may also be affected by sex differences; however, evidence is sparse. The present study aimed to explore the potential role of sex differences in the effect of extinction and reinstatement on behavioral functions in a rat model of PTSD. Fear learning was induced by three consecutive footshocks (0.8 mA, 3 s, paired with three sounds) on Day 1. Extinction training (20 sounds without footshock) was done 1 hr and 24 hr after footshocks. Reinstatement was done on Day 3, or 10, or 20, or 30, by placing rat in a new context and delivering one footshock (0.8 mA, 3 s, no sound). Results showed that females were more responsive to extinction due to significant decreases in freezing behavior in comparison with males, while reinstatement had more effect to recall shock-related memory in males. Pain threshold was increased and extinction decreased it in both sexes. Locomotion was decreased in fear conditioning group in both sexes and in PTSD + extinction males, while it was not changed in PTSD + extinction females. Reinstatement on Day 3 decreased locomotion in males. Rearing was decreased and extinction restored it in both sexes. By contrast, reinstatement on Day 3 decreased rearing in males. In conclusion, we suggested that females are more responsive to extinction and less sensitive to reinstatement. On the contrary, males are sensitive to reinstatement. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
