Corticotropin releasing factor type-1 receptor antagonism in the dorsolateral bed nucleus of the stria terminalis disrupts contextually conditioned fear, but not unconditioned fear to a predator odor
Date
2016-04-27
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Elsevier
Abstract
The bed nucleus of the stria terminalis (BNST) plays a critical role in fear and anxiety.
The BNST is important for contextual fear learning, but the mechanisms regulating this function
remain unclear. One candidate mechanism is corticotropin-releasing-factor (CRF) acting at CRF
type 1 receptors (CRFr1s). Yet, there has been little progress in elucidating if CRFr1s in the
BNST are involved in different types of fear (conditioned and/or unconditioned). Therefore, the
present study investigated the effect of antalarmin, a potent CRFr1 receptor antagonist, injected
intracerebroventricularly (ICV) and into the dorsolateral BNST (LBNST) during single trial
contextual fear conditioning or exposure to the predator odor 2,5-dihydro-2,4,5-
trimethylthiazoline (TMT). Neither ICV nor LBNST antalarmin disrupted unconditioned freezing
to TMT. In contrast, ICV and LBNST antalarmin disrupted the retention of contextual fear when
tested 24 hours later. Neither ICV nor LBNST antalarmin affected baseline or post-shock
freezing – indicating antalarmin does not interfere with the early phases of contextual fear
acquisition. Antalarmin did not (1) permanently affect the ability to learn and express contextual
fear, (2) change responsivity to footshocks, or (3) affect the ability to freeze. Our findings
highlight an important role for CRFr1s within the LBNST during contextually conditioned fear,
but not unconditioned predator odor fear.
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Author's final draft after peer review
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Citation
Asok, Arun, Schulkin, Jay, Rosen, Jeffrey B., Corticotropin releasing factor type-1 receptor antagonism in the dorsolateral bed nucleus of the stria terminalis disrupts contextually conditioned fear, but not unconditioned fear to a predator odor.Psychoneuroendocrinology http://dx.doi.org/10.1016/j.psyneuen.2016.04.021