A. Leslie Morrow, Ph.D.
Bowles Center for Alcohol Studies
John Andrews Distinguished Professor
Departments of Psychiatry and Pharmacology
UNC Neuroscience Center, Curriculum in Neurobiology, and Curriculum in Toxicology
Biosketch | Morrow Biosketch
Sex Specificity of Corticolimbic Circuit Activity and Anxiety-like Behavior After Alcohol Exposure
We are working with Dr. Melissa Herman at UNC to investigate the role of prelimbic prefrontal cortex (PrL) and central amygdala (CeA) regulation of both anxiety and alcohol dependence. We are examining sex-specific differences in PrL and CeA activity and anxiety-like behavior t baseline and following chronic ethanol exposure. In addition, we are examining the impact of allopregnanolone on ethanol-induced dysregulation. Funded by NIAAA.
Mechanisms of Brexanolone (Allopregnanolone) Therapeutics in Post-Partum Depression
Depression is associated with abnormal activation of inflammatory immune signals in the blood and the brain. We recently discovered that the endogenous steroid allopregnanolone inhibits these signals and therefore we hypothesize that this mechanism explains the therapeutic effects of the new drug Brexanolone, which is a proprietary form of allopregnanolone. We are working with Drs. Riah Patterson and Samantha Meltzer-Brody to investigate this idea in women with postpartum depression in hopes of discovering new ways to treat all forms of depression. Funded by the Foundation of Hope.
Clinical Trial to Assess Allopregnanolone Infusion during Alcohol Detoxification for Recovery from Withdrawal and Prevention of Relapse in Alcohol Use Disorder
We are working with Drs. David Goldman and Nancy Diaz-Granados and their team at NIAAA to investigate whether Brexanolone infusion will be an effective treatment for AUD detoxification by relieving ethanol withdrawal symptoms and preventing relapse through its anti-inflammatory actions in patient blood cells. Funded by NIAAA and Donations to UNC.
Allopregnanolone and THDOC Enhancement of Anti-Inflammatory Signals
We recently discovered that endogenous neuroactive steroids enhance the production of the ANTI-INFLAMMATORY mediators FRACKTALKINE and IL-10 in monocytes/macrophages and the brain. We are working to identify the pathways involved, the potency of various endogenous steroids, and the mechanism(s) of action. These studies will define a NOVEL mechanism of endogenous neurosteroid action on neuroimmune signaling with potential to alleviate inflammatory signaling associated with many neuropsychiatric diseases. Funded by Sage Therapeutics.
Biomarkers of Systemic Inflammation in Alcohol Use Disorder
We are working with Dr. Christian Hendershot at UNC to develop a biomarker assay of innate inflammation in blood cells of non-treatment seeking heavy drinkers who meet AUD criteria compared to light social drinkers and determine if allopregnanolone can inhibit the inflammatory signals or sensitivity to inflammatory activators in blood from these subjects. We will further determine the concentration of allopregnanolone necessary to block these signals in blood studied ex vivo. Funded by the Foundation of Hope.