The learned safety paradigm as a mouse model for neuropsychiatric research.

Fear conditioning is one of the most widely used animal models for studying the neurobiological basis of fear and anxiety states. Conditioned inhibition of fear (or learned safety), however, is a relatively unexplored behavioral paradigm addressing the aspect of regulation of fear, which is central to survival and mental health. Although fear conditioning is achieved by pairing a previously neutral, conditioned stimulus (CS) with an aversive, unconditioned stimulus (US), learned safety training consists of a series of explicitly unpaired CS-US presentations. Animals are trained for 3 d, one session per day, and learn to associate the CS with protection from the impending danger of the aversive events. The entire procedure can be completed within 7 d. The protocol has been successfully used to study the molecular underpinnings of a behavioral intervention for depression. This paradigm complements currently used animal tests in neuropsychiatric research addressing the dysregulation of emotional behaviors in genetic, pharmacological or environmental mouse models of human affective disorders.