CGRP antagonist infused into the bed nucleus of the stria terminalis impairs the acquisition and expression of context but not discretely cued fear

Calcitonin gene-related peptide (CGRP) infusions into the bed nucleus of the stria terminalis (BNST) evoke increases in startle amplitude and increases in anxiety-like behavior in the plus maze. Conversely, intra-BNST infusions of the CGRP antagonist CGRP8-37 block unconditioned startle increases produced by fox odor. Here we evaluate the contribution of CGRP signaling in the BNST to the development and expression of learned fear. Rats received five pairings of a 3.7-sec light and footshock and were tested for fear-potentiated startle one or more days later. Neither pre-training (Experiment 1) nor pre-test (Experiment 2) infusions of the CGRP antagonist CGRP8-37 (800 ng/BNST) disrupted fear-potentiated startle to the 3.7-sec visual cue. However, in both experiments, CGRP8-37 infusions disrupted baseline startle increases that occurred when rats were tested in the same context as that in which they previously received footshock (Experiment 3). Intra-BNST CGRP8-37 infusions did not disrupt shock-evoked corticosterone release (Experiment 4). These data confirm previous findings implicating BNST CGRP receptors in fear and anxiety. They extend those results by showing an important contribution to learned fear and, specifically, to fear evoked by a shock-associated context rather than a discrete cue. This pattern is consistent with previous models of BNST function that have posited a preferential role in sustained anxiety as opposed to phasic fear responses. More generally, the results add to a growing body of evidence indicating behaviorally, possibly clinically, relevant modulation of BNST function by neuroactive peptides.