The Role of the BNST in Stress and Alcohol-Related Behaviors
Open Access
- Author:
- Snyder, Angela
- Graduate Program:
- Neuroscience
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- September 02, 2021
- Committee Members:
- Nicholas Graziane, Major Field Member
Kirsteen Browning, Co-Chair & Dissertation Advisor
Blaise Peterson, Outside Unit & Field Member
Alistair Barber, Program Head/Chair
Yuval Silberman, Co-Chair & Dissertation Advisor - Keywords:
- norepinephrine
CRF
corticotropin releasing factor
CRH
beta-adrenergic receptor
beta2-adrenergic receptor
alcohol use disorder
substance use disorder
stress
AUD
relapse
alcohol
alcohol use
corticotropin releasing hormone - Abstract:
- Alcohol Use Disorder (AUD) is a chronic and relapsing disease that affects around 14.5 million individuals in the United States, and about 16 million Americans use alcohol heavily. Stress is often cited as a key trigger to harmful alcohol use and relapse into drinking, and thus provides a major obstacle in the prevention and treatment of AUD. Two major molecules involved in the physiological stress response include corticotropin releasing factor (CRF) and norepinephrine (NE). An important brain region associated with behavioral responses to stress and alcohol-related behaviors is the bed nucleus of the stria terminalis (BNST), and CRF and NE in the BNST are implicated in mediating such behaviors. Further, the BNST is separated into numerous subregions that differ in their cytoarchitecture and function, and two major subregions of interest are the dorsal BNST (dBNST) and ventral BNST (vBNST). Evidence suggests that stress-related and drug-seeking behaviors are mediated via CRF and NE in the dBNST and vBNST, but through different pathways and mechanisms. For example, the beta1-adrenergic receptor (β1-AR) is implicated in dBNST control of excitatory neurotransmission via CRF; however, the vBNST mediates stress-related drug-seeking behavior via a mechanism involving the β2-AR specifically. This dissertation explores CRF and β-AR mediated glutamatergic transmission in the dBNST and vBNST after alcohol or stress exposure. BNST subregional differences and neurocircuitry changes after stress and alcohol exposure are uncovered. A novel mouse model of stress-enhanced drinking after a period of forced abstinence was also developed and used to further investigate BNST CRF and NE’s role in stress-related alcohol use. Ultimately, investigating the neurocircuitry changes involved in stress and alcohol use is useful for the development of future prevention and treatment options for AUD.