Male and female mice showed no effect of prefrontal PICK1 knockdown (KD) on the time to reach extinction criterion (A). However, PICK1 KD in the mPFC of male mice led to a significant decrease in active responses during cue-induced reinstatement [B, F(1,20)= 4.44, *p<0.01, n=10–12/group]. In contrast, PICK1 KD in the mPFC of female mice led to an increase in active responses during cue-induced reinstatement [C, interaction: F(1,19)= 4.87, *p<0.01, n=9–13/group].