Mark Brodie received his bachelor’s degree in Biological Sciences from Northwestern University in 1979 and his PhD in Pharmacology from the University of Illinois at Chicago in 1984. After postdoctoral training in Denver, CO in the laboratory of Dr. Thomas Dunwiddie, Dr. Brodie returned to the Chicago area and worked as a research scientist at Abbott Laboratories for four years. In 1990, Dr. Brodie joined the Department of Physiology and Biophysics as a Research Assistant Professor in the laboratory of Dr. Sarah Appel (Sarah Shefner) and is currently a Professor in this department. He currently serves as the Scientific Director of the Center for Alcohol Research in Epigenetics (CARE; Director Subhash C. Pandey) as well as the Director of Graduate Studies of the Department of Physiology and Biophysics.

For more than 30 years, I have led a program of NIH-funded research studying the acute and chronic actions of alcohol on dopaminergic neurons of the ventral tegmental area (VTA). As the VTA is a key brain region involved in the rewarding and reinforcing effects of alcohol and drugs of abuse, my work addresses problems of alcoholism and possible therapeutic interventions by studying the effects of alcohol at the cellular level. I have a long and on-going interest in understanding how physiological functions in the VTA are altered by alcohol, and in identifying factors that can regulate those alcohol actions. Recent studies in my laboratory, in collaboration with Dr. Subhash Pandey and the Center for Alcohol Research in Epigenetics (CARE), have explored the regulation by histone deacetylases (and other epigenetic factors) of GABA function in the VTA during alcohol withdrawal. The focus on epigenetic changes induced by alcohol in the VTA now directs most of my work, and all my research is directed toward understanding alcohol effects on the brain in order to provide a foundation for development of more effective treatment of alcoholism.

Acute actions of alcohol: In collaboration with Sarah Appel, I have explored the acute action of ethanol to excite neurons of the ventral tegmental area. Our work (published in 1990 in collaboration with Dr. Thomas Dunwiddie) was the first observation of ethanol excitation of VTA neurons in vitro. Ethanol also increases the firing rate of VTA neurons under conditions that block calcium-dependent synaptic transmission; the first intracellular studies of actions of alcohol on VTA neurons was published in collaboration with Dr. Appel in 1998. We later (1999) demonstrated that ethanol excites acutely isolated dopaminergic VTA neurons, again indicating that ethanol directly stimulates these neurons. In 2019, my laboratory published the first landmark paper on a novel specific potassium channel, KCNK13, that plays a crucial role in the VTA in mediating neuronal excitation by ethanol and in regulating binge drinking.

Chronic and epigenetic effects of alcohol: I have studied the action of repeated ethanol exposure on the physiological responses of VTA neurons of mice and rats. Mine was the first publication (2002) to demonstrate that withdrawal following repeated exposure to ethanol produced an increase in the acute excitatory effect of ethanol on VTA neurons. This was the first electrophysiological demonstration anywhere that withdrawal following repeated ethanol exposure could cause an increased responsiveness to the effects of ethanol. My laboratory also demonstrated that withdrawal from repeated exposure to ethanol caused a decrease in the response of VTA neurons to the inhibitory neurotransmitter GABA. In vitro or in vivo treatment with histone deacetylase (HDAC) inhibitors normalized the response to GABA during withdrawal. Our comprehensive study of GABA hyposensitivity of VTA neurons during withdrawal demonstrated that this phenomenon is associated with a decreased expression of genes for cholesterol synthesis enzymes, and GABA hyposensitivity during withdrawal could be rescued by administration of exogenous cholesterol. These studies are ongoing thanks to the generosity of the NIAA and the CARE. Ultimately, understanding these epigenetic mechanisms of brain changes during withdrawal can lead to therapies that can reduce alcohol craving and can more effectively treat alcohol use disorder.