Activation of gastrin-releasing peptide receptors at the infralimbic cortex elicits gastrin-releasing peptide release at the basolateral amygdala: Implications for conditioned fear

The basolateral amygdala (BLA) and infralimbic (IL) cortex share strong reciprocal interconnections and are key structures in conditioned fear circuitry. Gastrin-releasing peptide (GRP) or its receptor antagonists can modulate the conditioned fear response when exogenously administered at either of these sites, and increased release of GRP at the BLA occurs in response to conditioned fear recall. The present study sought to determine whether a functional pathway utilizing GRP exists between the IL cortex and BLA and whether this pathway is also influenced by amygdala corticotropin-releasing factor (CRF) release. To this end, we assessed the effects of intra-IL cortex injection of GRP or GRP co-administered with a receptor antagonist, RC-3095, on the downstream release of GRP and/or CRF at the BLA. Results showed that microinjection of GRP at the IL cortex increased the release of GRP, but not CRF, at the BLA, an effect blocked by co-administration of RC-3095. Administration of RC-3095 into the IL cortex on its own, however, also elicited the release of GRP (but not CRF) at the BLA. These findings suggest that a functional pathway utilizing GRP (among other factors) exists between the IL cortex and BLA that may be relevant to conditioned fear, but that GRP and CRF do not interact within this circuitry. Moreover, the finding that the release profile of GRP was similar following administration of either GRP or its receptor antagonist, lends support to the view that RC-3095 has partial agonist properties. Together these findings provide further evidence for the involvement of GRP in fear and anxiety-related disorders.