The Nixon laboratory focuses on novel mechanisms of and drug discovery for neuropathology in alcohol use disorders (AUD). This two-prong approach of novel target identification coupled with drug discovery has allowed us to make seminal discoveries in new mechanisms that contribute to brain damage and recovery in alcohol use disorders, then use those discoveries to drive the development of novel approaches for the treatment of alcohol use disorders.

Alcohol use disorder (AUD) is a growing public health problem though pharmacological treatments are not widely successful.  People drink to excess for a variety of reasons necessitating a variety of approaches for successful treatment. The majority of pharmacological treatments for AUDs target motivational behaviors of drug use, but targeting this aspect of abuse/addiction alone has not been widely successful. We continue to take the novel approach of examining neuroprotective agents that promote plasticity in order to repair or protect the brain from alcohol-induced damage.

One region of alcohol neurotoxicity is in behavioral control circuitry which includes the hippocampus and prefrontal cortex. We hypothesize that damage to this circuit essentially releases a brake on the dysfunctional, compulsive drive of the mesolimbic dopamine system.  Thus, the Nixon Lab has focused on two mechanistic areas relevant to hippocampal structure and function: (1) the role of adult neural stem cells in alcoholic neuropathology and recovery in abstinence and (2) the role microglia play in the adolescent’s enhanced susceptibility to developing an alcohol use disorder.

Our third area encompasses our collaborative drug discovery work, which has focused heavily on novel neuroprotectants but also target-agnostic screening of novel compounds and natural products to treat alcohol and nicotine co-abuse.

Approaches utilize novel or state-of-the-art histological, biochemical and behavioral techniques in ex vivo, in vitro and in vivo models of AUDs.

Nixon, K. & Mangieri, R.A. (2019). Compelled to drink: Why some cannot stop. Science 366 (6468): 947 – 948.  DOI: 10.1126/science.aaz7357

Maggio, S.E., Saunders, M.A., Nixon, K., Prendergast, M.A., Zheng, G., Crooks, P., Dwoskin, L.P.,  Bell, R.L., Bardo, M.T. (2018).  An improved model of ethanol and nicotine co-use in female P rats: Effects of naltrexone, varenicline, and the selective nicotinic <alpha>6<beta>2* antagonist r-bPiDI. Drug and Alcohol Dependence, 193: 154-161 PMC6239925.

Maggio, S.E., Saunders, M.A., Baxter^, T.A., Nixon, K., Prendergast, M.A., Zheng, G. Crooks, P. Dwoskin, L.P., Slack, R.D., Newman, A.H., Bell, R.L., & Bardo^, M.T. (2018). Effects of the Nicotinic Agonist Varenicline, Nicotinic Antagonist r-bPiDI, and DAT Inhibitor (R)-Modafinil on Co-use of Ethanol and Nicotine in Female P Rats. Psychopharmacology, 235(5):1439-1453. PMC6058964. 

Hayes, D.M., Geil Nickell, C.R., Chen, K.Y., Heath, M.M., McClain, J.A., Deeny, M.A., & Nixon, K. (2018).Activation of neural stem cells from quiescence drives reactive hippocampal neurogenesis after alcohol dependence. Neuropharmacology, 133: 276-288. PMC6620048. 

Geil Nickell C.R., Peng, H., Hayes D.M., Chen, K. McClain J.A., & Nixon K. (2017). Type 2 neural progenitor cell activation drives reactive neurogenesis after binge-like alcohol exposure in adolescent, male rats. Invited submission for special issue on adolescence. Frontiers in Psychiatry8:283. doi: 10.3389/fpsyt.2017.00283 PMC5736541.

Peng, H., Nickell, C.R.G., Chen, K.Y., McClain, J.A., & Nixon K. (2017). Increased expression of M1 and M2 phenotypic markers in isolated microglia after four-day binge alcohol exposure in male rats.Alcohol 62: 29 - 40. PMC5695703.

McClain, J.A., Morris, S.A. & Nixon, K. (2014). Ectopic hippocampal neurogenesis in adolescent ratsfollowing alcohol dependence.  Addiction Biology, 19: 687-99. PMC23844726

Marshall, S.A., McClain, J.A., Kelso, M.L., Hopkins, D.M., Pauly, J.R. & Nixon, K. (2013).  Microglial activation is not equivalent to neuroinflammation: the importance of microglia phenotype in alcohol-induced neurodegeneration.  Neurobiology of Disease, 54, 239-251.  PMC3629000

McClain, J.A., Hayes, D.M., Morris, S.A. & Nixon, K. (2011).  Adolescent binge alcohol exposure alters hippocampal progenitor cell proliferation in rats: Effects on cell cycle kinetics. Journal of Comparative Neurology, 519, 2697-2710. PMC3454493

McClain, J.A., Morris, S.A., Deeny, M.A., Marshall, S.A., Hayes, D.M., Kiser, Z.M. & Nixon, K. (2011).  Adolescent binge alcohol exposure induces long-lasting partial activation of microglia. Brain Behavior and Immunity, 25, S120–S128. PMC3098298

Morris, S.A., Eaves, D.W., Smith, A.R. & Nixon, K. (2010). Inhibition of adult neurogenesis - a mechanism of hippocampal neurodegeneration in an adolescent alcohol abuse model. Hippocampus 20, 596-607. PMC2861155

Nixon, K., Kim, D.H., Potts, E.N., He, J. & Crews, F.T. (2008). Distinct cell proliferation events during abstinence after alcohol dependence: microglia proliferation precedes neurogenesis.

Nixon, K. & Crews, F.T. (2004).  Temporally specific burst in cell proliferation increases hippocampal neurogenesis in protracted abstinence from alcohol.  The Journal of Neuroscience 24, 9714-9722.

Nixon, K. & Crews, F.T. (2002).  Binge alcohol exposure decreases neurogenesis in adult rat hippocampus.  Journal of Neurochemistry 83, 1087-1093.

Check out our new book chapters:

Melbourne, J., Thompson, K.R., Peng H., & Nixon, K. (2019). Its complicated: The relationship between alcohol and microglia in the search for novel pharmacotherapeutic targets for alcohol use disorders. In Shafiqur Rahman (Ed.) Molecular Basis of Neuropsychiatric Disorders: from Bench to Bedside inProgress in Molecular Biology and Translational Science, 167, 179-221.

Olsufka, R. Peng, H. Newton, J. & Nixon, K. (2018). Alcohol Effects on Adult Neural Stem Cells – A Novel Mechanism of Neurotoxicity and Recovery in Alcohol Use Disorders.  Invited submission for T. Rasmussen (Ed.) Stem Cells in Birth Defects Research and Developmental Toxicology. John Wiley and Sons (New York).