Predator threat induces behavioral inhibition, pituitary-adrenal activation and changes in amygdala CRF-binding protein gene expression

Abstract

SummaryBehavioral inhibition (BI) is an adaptive defensive response to threat; however, extreme BI is associated with anxiety-related psychopathology. When rats are exposed to a natural predator they display stress-and anxiety-related behavioral alterations and physiological activation. To develop a preclinical rodent model to study mechanisms underlying human BI and anxiety, we examined the extent to which ferret exposure elicits anxiety-related BI and HPA and amygdala activation of the CRF system. In the first experiment, BI and other behaviors were assessed in the presence or absence of a ferret. In the second experiment, ferret-induced corticosterone release and changes in brain cfos expression were assessed. In the final experiment, gene chip and quantitative real time-PCR analyses were performed on amygdala tissue from control and ferret-exposed rats. Ferret exposure increased BI and submissive posturing, as well as plasma corticosterone and the number of Fospositive cells in several brain regions including the amygdala. Gene expression analysis revealed increased amygdalar mRNA for CRF-binding protein, but not the CRF 1 receptor, CRF 2 receptor or CRF. In rodents, ferret exposure can be used to elicit anxiety-related BI, which is associated with HPA and amygdala activation. Since the amygdala and the CRF system have been implicated in adaptive and maladaptive anxiety responses in humans, these data support use of our rodent model to further investigate mechanisms underlying anxiety-related psychopathology in humans.

Corticotropin-Releasing Factor in the Basolateral Amygdala Enhances Memory Consolidation via an Interaction with the -Adrenoceptor-cAMP Pathway: Dependence on Glucocorticoid Receptor Activation

“…dependent enhancement of 48 h inhibitory avoidance retention performance and that the effects depend on interactions with the noradrenergic system of the BLA and require concurrent GR activation. Immediate posttraining infusions of CRF 6 -33 administered into the BLA, which contains a high level of CRF-BP (Herringa et al, 2004;Roseboom et al, 2007), dose-dependently enhanced inhibitory avoidance retention latencies. Consistent with the findings of many previous pharmacological studies of memory, whereas moderate doses of CRF 6 -33 enhanced retention performance, lower and higher doses were ineffective.…”

Fear is the mother of invention: anuran embryos exposed to predator cues alter life-history traits, post-hatching behaviour, and neuronal activity patterns

“…Indeed, it remains to be elucidated whether and how the observed altered activity patterns in MCs actually translate in the inhibition of muscular fibres resulting in tadpole behavioural freezing. Admittedly, amphibians present strong synaptic connections between the olfactory bulb and the amygdala (Herrick, 1921;Moreno et al, 2005), which plays a crucial role in their fear behaviour as described for mammals (Roseboom et al, 2007).…”

Brain Transcriptomic Response of Threespine Sticklebacks to Cues of a Predator

“…Comoli et al, 2003;Blanchard et al, 2005;Motta et al, 2009], are upregulated in the brain in response to the threat of predation. For example, corticotropin-releasing factor genes were upregulated in the amygdala of rats 3 h after a 10-min exposure to a ferret predator [Roseboom et al, 2007].…”

“…The power of genomics has only recently been applied to understand the coordinated action of the entire transcriptome in response to predation [but see Wang et al, 2003;Roseboom et al, 2007]. Whole-genome surveys are an attractive strategy because it is likely that the response to threat of predation involves multiple interacting genes and pathways.…”