Corticotropin Releasing Hormone Signaling in the Bed Nuclei of the Stria Terminalis as a Link to Maladaptive Behaviors

Abstract

The bed nuclei of the stria terminalis (BST) is a limbic region in the extended amygdala that is heavily implicated in anxiety processing and hypothalamic-adrenal-pituitary (HPA) axis activation. The BST is complex, with many nuclei expressing different neurotransmitters and receptors involved in a variety of signaling pathways. One neurotransmitter that helps link its functions is corticotropin releasing hormone (CRH). BST CRH neuron activation may cause both anxiogenic and anxiolytic effects in rodents, and CRH neurons interact with other neuron types to influence anxiety-like responses as well as alcohol and drug–seeking behavior. This review covers the link between BST CRH neurons and thirteen other neurotransmitters and receptors and analyzes their effect on rodent behavior. Additionally, it covers the translational potential of targeting CRH signaling pathways for the treatment of human mental health disorders. Given the massive impact of anxiety, mood, and substance use disorders on our society, further research into BST CRH signaling is critical to alleviate the social and economic burdens of those disorders.

Long‐lasting mechanical hypersensitivity and CRF receptor type‐1 neuron activation in the BNST following adolescent ethanol exposure

“…Rodent studies show that cells in the BNST express a variety of neuropeptides and neuropeptide receptors that modulate the activity of BNST cells (Kash et al., 2015). Remarkably, the BNST AL has emerged as an important site of action for the neuropeptide corticotropin‐releasing factor (CRF) in potentiating the stress response (Young & Tong, 2021), and dysfunction of this CRF system contributes to the etiology of several psychiatric disorders, including depression (Crestani et al., 2010), anxiety disorders (Walker et al., 2009), and addiction (Koob, 2010). CRF application increases the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in BNST AL neurons, an effect that is blocked by a selective CRF type‐1 receptor (CRFR1) antagonist (Kash et al., 2008).…”

Artificial Intelligence Identified Resilient and Vulnerable Female Rats After Traumatic Stress and Ethanol Exposure: Investigation of Neuropeptide Y Pathway Regulation

“…Y1R and Y2R are found in regions of the amygdala and extended amygdala including the basolateral amygdala (BLA), central nucleus of the amygdala (CeA), and bed nucleus stria terminalis (BNST; Tasan et al, 2016 ; Wood et al, 2016 ; Mackay et al, 2019 ). These regions were chosen for this study because they are critical for fear- and anxiety-related behaviors and ethanol consumption ( Hawley et al, 2010 ; Gilpin et al, 2015 ; Pleil et al, 2015 ; Langevin et al, 2016 ; Young and Tong, 2021 ).…”