UVM Theses and Dissertations
Format:
Print
Author:
Lezak, Kimberly R.
Dept./Program:
Psychology
Year:
2013
Degree:
PhD
Abstract:
Exposure to traumatic or chronic stress promotes a variety of physiological and psychological consequences, including anxiety disorders like post-traumatic stress disorder (PTSD). Recently, alterations in pituitary adenylate cyclaseactivating polypeptide (PACAP) expression and genes associated with its cognate PAC1 receptor were found to be associated with diagnosis of PTSD. The bed nucleus of the stria terminalis (BNST) is important in mediating anxiety as well as regulating activity in the hypothalamic- pituitary- adrenal (HPA) axis. Importantly, increases in BNST PACAP and PAC1 receptor expression as well as increases in anxiety-like behavior are observed in rats following exposure to repeated variate stress. Intra-BNST PACAP infusion mimics many of the behavioral consequences of stressor exposure, including anxorexia and anxiety like behavior.
Hence, BNST PACAP activation may also playa critical role in regulating the HPA axis. The current studies examined the functional and anatomical connectivity between BNST PACAP and activity in the HPA axis. In the first study, we determined that increase BNST PACAP signaling increased HPA axis activation, since the infusion of PACAP into the BNST was able to increase plasma corticosterone levels for up to 60 minutes following infusion. We then examined the anatomical connectivity through which BNST PACAP could alter HPA axis activity through use of retrograde and anterograde tracer techniques targeted to the BNST and hypothalamus.
Results from this study replicate previous findings demonstrating that cells in the ventral BNST project to the hypothalamus. Finally, we found that increases in BNST PACAP in response to stress exposure take time develop, and glucocorticoids may work together with other stress related mechanisms to produce increases in BNST PACAP transcript. The results from these studies suggest a circuit through which interactions between BNST PACAP and the HPA axis may contribute to maladaptive behavioral and physiological responding in stress related mental health disorders.
Hence, BNST PACAP activation may also playa critical role in regulating the HPA axis. The current studies examined the functional and anatomical connectivity between BNST PACAP and activity in the HPA axis. In the first study, we determined that increase BNST PACAP signaling increased HPA axis activation, since the infusion of PACAP into the BNST was able to increase plasma corticosterone levels for up to 60 minutes following infusion. We then examined the anatomical connectivity through which BNST PACAP could alter HPA axis activity through use of retrograde and anterograde tracer techniques targeted to the BNST and hypothalamus.
Results from this study replicate previous findings demonstrating that cells in the ventral BNST project to the hypothalamus. Finally, we found that increases in BNST PACAP in response to stress exposure take time develop, and glucocorticoids may work together with other stress related mechanisms to produce increases in BNST PACAP transcript. The results from these studies suggest a circuit through which interactions between BNST PACAP and the HPA axis may contribute to maladaptive behavioral and physiological responding in stress related mental health disorders.