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Allopregnanolone induces state-dependent fear via the bed nucleus of the stria terminalis

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&NA; Gonadal steroids and their metabolites have been shown to be important modulators of emotional behavior. Allopregnanolone (ALLO), for example, is a metabolite of progesterone that has been linked to… Click to show full abstract

&NA; Gonadal steroids and their metabolites have been shown to be important modulators of emotional behavior. Allopregnanolone (ALLO), for example, is a metabolite of progesterone that has been linked to anxiety‐related disorders such as posttraumatic stress disorder. In rodents, it has been shown to reduce anxiety in a number of behavioral paradigms including Pavlovian fear conditioning. We have recently found that expression of conditioned contextual (but not auditory) freezing in rats can be suppressed by infusion of ALLO into the bed nucleus of the stria terminalis (BNST). To further explore the nature of this effect, we infused ALLO into the BNST of male rats prior to both conditioning and testing. We found that suppression of contextual fear occurred when the hormone was present during either conditioning or testing but not during both procedures, suggesting that ALLO acts in a state‐dependent manner within the BNST. A shift in interoceptive context during testing for animals conditioned under ALLO provided further support for this mechanism of hormonal action on contextual fear. Interestingly, infusions of ALLO into the basolateral amygdala produced a state‐independent suppression of both conditioned contextual and auditory freezing. Altogether, these results suggest that ALLO can influence the acquisition and expression of fear memories by both state‐dependent and state‐independent mechanisms. HighlightsIntra‐BNST allopregnanolone induces state‐dependent fear for context but not tone.Intra‐BNST allopregnanolone enhances fear acquisition.Intra‐BNST allopregnanolone functions as an interoceptive feature of context.Intra‐BLA allopregnanolone impairs contextual and cued fear.BNST state may contribute to context during fear acquisition.

Keywords: state; fear; state dependent; bed nucleus; nucleus stria; allopregnanolone

Journal Title: Hormones and Behavior
Year Published: 2017

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