Kimberly Nixon, Ph.D. (left) and Regina Mangieri, Ph.D. (right).
Two faculty members in The University of Texas at Austin College of Pharmacy recently contributed an article to the prestigious magazine Science discussing exciting new findings in alcohol use disorder (AUD) research. Associate Professor and James T. Doluisio Centennial Fellow Kimberly Nixon, Ph.D. and Research Assistant Professor Regina Mangieri, Ph.D. write about the discoveries that show individual differences in the activity of neurons that comprise a newly described brain circuit in mice during early alcohol experience. Drs. Nixon and Mangieri work in the Division of Pharmacology and Toxicology and their research focuses pertain to alcohol’s effect on the brain with the goal of discovering new medications for treating AUDs.
The article, “Compelled to drink: Why some cannot stop,” considers recent findings by researchers Siciliano et al. that discovered individual differences in the activity of neurons in a frontal cortex to brain stem circuit that predicts the later escalation of alcohol drinking to compulsive intake in a mouse model. “These findings were truly exciting,” says Dr. Nixon. “Compulsive alcohol drinking (drinking despite negative consequences) is the defining characteristic of a severe AUD. These researchers not only defined a new brain circuit involved in compulsive drinking, but showed individual differences at the level of electrical activity in the neurons that comprise this circuit. The individual differences in electrical activity predicted which mice would go on to drink compulsively after a binge-like drinking episode despite drinking the same amount of alcohol during that episode.”
According to Dr. Mangieri, “this research group previously found that this circuit is important for responses to aversive events, and they have now asked why aversive outcomes don’t deter everyone from drinking alcohol. These new findings point to a neurological explanation for why only some mice continue to drink alcohol even when it comes with negative consequences. They found these differences in circuit activity before mice developed compulsive drinking behavior. In other words, some mice had a biological predisposition that made them susceptible to developing alcohol drinking behaviors that are similar to humans with AUD.”
Nixon notes that “this work has important implications. For one, it has potential as a biomarker of propensity to develop severe AUD based on this electrical activity. Second, the discovery of this circuit’s role in compulsive drinking suggests that there may be novel pharmacological targets that could be identified and developed for the treatment of AUDs.”
The Nixon laboratory focuses on novel mechanisms of and drug discovery for alcoholic neuropathology. This two-prong approach of novel target identification coupled with drug discovery has allowed the lab to make seminal discoveries in new mechanisms that contribute to not only brain damage but also recovery mechanisms in AUDs, then use those discoveries to drive the development of novel approaches for the treatment of AUDs. Dr. Nixon’s lab is housed in the Division of Pharmacology and Toxicology and is a member of the Waggoner Center for Alcohol and Addiction Research.
The Mangieri laboratory studies how alcohol changes physiological processes and cell-to-cell communication in the brain, and is particularly interested in immune-nervous system interactions that drive excessive alcohol drinking. Dr. Mangieri’s lab is housed in the Division of Pharmacology and Toxicology and is a member of the Waggoner Center for Alcohol and Addiction Research and the Center for Molecular Carcinogenesis and Toxicology.