Journal
PEPTIDES
Volume 142, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2021.170554
Keywords
PACAP; Stress; Anxiety; Pain; Bed nucleus of stria terminalis; Amygdala; Parabrachial nucleus; Prefrontal cortex; Hippocampus
Funding
- National Institute of Mental Health (NIMH) [MH097988]
- National Institute of General Medical Sciences (NIGMS) [GM129431]
- University of Vermont (UVM) Vice President for Research Office
- UVM College of Arts and Sciences
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PACAP is a pleiotropic polypeptide that activates G protein-coupled receptors and is widely distributed in the nervous system. It plays roles in regulating fear memories, anxiety-like behavior, and emotional pain. Outside of the CNS, PACAP may also participate in stress responses by modulating the HPA axis.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic polypeptide that can activate G protein-coupled PAC1, VPAC1, and VPAC2 receptors, and has been implicated in stress signaling. PACAP and its receptors are widely distributed throughout the nervous system and other tissues and can have a multitude of effects. Human and animal studies suggest that PACAP plays a role responding to a variety of threats and stressors. Here we review the roles of PACAP in several regions of the central nervous system (CNS) as they relate to several behavioral functions. For example, in the bed nucleus of the stria terminalis (BNST), PACAP is upregulated following chronic stress and may drive anxiety-like behavior. PACAP can also influence both the consolidation and expression of fear memories, as demonstrated by studies in several fear-related areas, such as the amygdala, hippocampus, and prefrontal cortex. PACAP can also mediate the emotional component of pain, as PACAP in the central nucleus of the amygdala (CeA) is able to decrease pain sensitivity thresholds. Outside of the central nervous system, PACAP may drive glucocorticoid release via enhanced hypothalamic-pituitary-adrenal axis activity and may participate in infection-induced stress responses. Together, this suggests that PACAP exerts effects on many stress-related systems and may be an important driver of emotional behavior.
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