Acute inescapable stress alleviates fear extinction recall deficits caused by serotonin transporter abolishment

Life stress increases risk for developing post-traumatic stress disorder (PTSD), and more prominently so in short-allele carriers of the serotonin transporter linked polymorphic region (5-HTTLPR). Serotonin transporter knockout (5-HTT^−/−) rats show compromised extinction (recall) of conditioned fear, which might mediate the increased risk for PTSD and reduce the therapeutic efficacy of exposure therapy. Here, we assessed whether acute inescapable stress (IS) differentially affects fear extinction and extinction recall in 5-HTT^−/− rats and wildtype controls. Surprisingly, IS experience improved fear extinction recall in 5-HTT^−/− rats to the level of wildtype animals, while wildtypes were unaffected by this IS. Thus, whereas 5-HTT^−/− rats evidently were more responsive to the stressor, the behavioral consequences presented themselves as adaptive.