There is high comorbidity between the prevalence of post-traumatic stress disorder (PTSD) and alcohol use disorders (AUD) and this is a growing research area of interest. Current animal models have led to important insights into the neural circuits and molecular mechanisms involved in PTSD alone. However, despite the prevalence of AUD in patients with PTSD, there is a knowledge gap regarding the underlying neurobiology of comorbidity. This is due, in part, to the lack of animal models assessing the co-occurrence of PTSD and alcohol misuse. This is a critical topic, as validated animal models can lead to a better mechanistic understanding of the co-occurrence of these disorders, which may ultimately lead to more effective treatment strategies. In this application, we will combine a predator odor (PO) exposure model of PTSD with alcohol self- administration to model the emergence of maladaptive drinking patterns following development of PTSD from a traumatic experience. Studies in Aim 1 will focus on establishing and validating an animal model of PTSD and alcohol self-administration, along with cutoff behavioral criteria for use in the model. Studies in Aim 2 will probe adaptations in the Group II family of regulatory metabotropic glutamate receptors (mGluR2/3) as there is growing evidence for glutamatergic dysregulation in both PTSD and AUD. Studies in Aim 3 will focus on examining neural circuitry involving the nucleus reuniens, a midline thalamic nucleus, that has been emerging in the glutamatergic circuitry and symptom profile of PTSD, stress and depression. These studies represent an innovative strategy to advance understanding of mechanisms underlying susceptibility to increased alcohol drinking in PTSD.

Public Health Relevance

There is high comorbidity between the prevalence of post-traumatic stress disorder (PTSD) and alcohol use disorders (AUD). The studies in this application will validate an animal model of PTSD and escalated alcohol drinking. Studies will also explore methods by which to reduce the escalations in drinking by examining neurobiological and neurocircuitry changes that occur following PTSD. Together these studies aim to better understand the neurobiological underpinnings of PTSD and alcohol drinking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA026537-01
Application #
9485726
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Grakalic, Ivana
Project Start
2017-09-12
Project End
2022-06-30
Budget Start
2017-09-12
Budget End
2018-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Psychiatry
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Makhijani, Viren H; Van Voorhies, Kalynn; Besheer, Joyce (2018) The mineralocorticoid receptor antagonist spironolactone reduces alcohol self-administration in female and male rats. Pharmacol Biochem Behav 175:10-18