| Corticotropin-releasing factor (CRF) is a key mediator of the stress response, and dysregulation of the CRF system is thought to occur in psychopathology such as depression. CRF binds two receptors and a CRF-binding protein (CRF-BP), which may inactivate or modulate the actions of CRF at its receptors. The amygdala is an important anatomical substrate for CRF and contains CRF, its receptors, and CRF-BP. The role of CRF-BP in modulating CRF and responses to stress has been an understudied topic. An examination of the regulation and role of CRF-BP during and following stress is crucial for understanding adaptations and maladaptations of the CRF system in response to stress. This thesis aims to further our knowledge in this area with a specific focus on amygdala CRF-BP. In a series of studies, we show that acute, but not repeated, stress increases basolateral amygdala (BLA) CRF-BP mRNA. Subsequent studies mapped the time course of this increase and revealed that other components of the CRF system in the amygdala remained unchanged. We then examined potential regulatory factors responsible for stress-induced increases in BLA CRF-BP, namely corticosterone and CRF. CRF, but not corticosterone, was able to increase BLA CRF-BP mRNA, an effect which may take place through a novel mechanism. Studies exploring the behavioral function of amygdala CRF-BP remained inconclusive, likely due to the unclear mechanism of action for drugs thought to inhibit CRF-BP. Finally, we examined whether the expression of amygdala CRF-BP is altered in psychopathology. This was performed in a post mortem study of schizophrenia, bipolar disorder, and major depression with matched controls. The anatomical distribution of human CRF-BP was described for the first time. Levels of CRF-BP gene expression were compared among the four conditions. While significant differences in BLA CRF-BP were evident among groups, experimenters remained blinded to group condition at the time of writing. Together, the studies in this thesis provide new insight into the regulation and possible role of amygdala CRF-BP in stress and psychopathology. |
