John R. Andrews Distinguished Professor, Departments of Psychiatry and Pharmacology
UNC Hospitals – Chapel Hill
Education and Training:
Dr. Breese’s research relates to defining the role of stress in the negative affect, changes in brain functional magnetic resonance imaging (fMRI), and craving in abstinent alcoholics not seen in social drinkers. To model the stress induced negative affect during alcohol abstinence, chronic intermittent alcohol (CIA) exposure induces an enduring adaptation that sensitizes stress-induced negative affect during abstinence—an outcome consistent with the kindling/stress hypothesis of alcoholism. However, research to define the neural basis of stress induced changes that occur in abstinent alcoholics has been neglected. While corticotropin releasing factor (CRF) acting in the central amygdala (CeA) contributes to stress-induced negative affect after CIA, other inputs synapse on CeA neurons including basolateral-amygdala glutamate terminals, hypothalamic-oxytocin terminals, and vasopressin terminals. Unknown is the role these other CeA inputs have in facilitating stress-induced negative affect after CIA exposure. Likewise unidentified is whether CeA medial division (CEM) neurons that output terminals to the periaqueductal gray and other brain sites are a component of the neural circuit supporting the stress-induced anxiety that follows CIA treatment. To guide addressing these unknowns, the hypothesis tested is that stress facilitates anxiety during abstinence from CIA exposure by influencing a neural circuit composed of terminal inputs to the CeA-lateral (CEL) and CEM divisions which modulate CEM output. Techniques to pursue this hypothesis include use of behavior, biochemistry, optogenetics, electrophysiology, and pharmacology. New knowledge defining CIA adaptation influences on these circuits that may facilitate stress-induced negative affect could possibly provide clues by which to minimize the barrier to developing improved therapeutics to treat stress-induced negative symptoms observed in abstinent alcoholics.