Research in my laboratory is directed toward a better understanding of the molecular mechanisms that underlie addiction and improved treatment of substance use disorders.
Substance use disorders have a devastating impact on individuals and their families, with substantial medical and societal impact. Alcoholism is associated with disruptions in circadian rhythms that persist during abstinence and increase risk for relapse. Additionally, genetic variations (SNPs or mutations) in circadian genes have been shown to modulate alcohol consumption, anxiety, depression, and mania in humans. Pre-clinical studies have also revealed that circadian mutations in homologous circadian transcription factors, CLOCK and NPAS2, can alter drug sensitivity and mood-related behaviors. We carry out studies to directly address how brain region and cell specific expression of these genes affects mood- and drug-related behaviors. Findings from these studies will have important translational significance by contributing to our understanding of vulnerability for substance use disorders and susceptibility to relapse.
Substance use disorders are characterized by inability to control intake and high rates of relapse. There exists a serious public health need to identify and characterize new and more effective treatments. Therapies that increase neuronal activity in the nucleus accumbens (NAc) are emerging as a promising treatment tool for alcohol use disorders. However, further research is needed to determine behavioral and molecular consequences of increasing specific brain activity. I am addressing this gap in our knowledge by using genetic and pharmacological approaches to determine the effects of chronic NAc stimulation on the rewarding and aversive aspects of alcohol behaviors, as well as identify treatment responsive gene networks and specific circuitry that underlie lasting reductions in alcohol intake. Findings will provide a great deal of insight into mechanisms underlying the effectiveness of new potential therapies for alcohol use disorders.
My long-term career goals are to move science forward by contributing to the understanding of the molecular mechanisms that underlie addiction and to improved treatment of substance use disorders. Despite advances in neuroscience and psychiatry, we have much to gain in our understanding of substance use disorders and the development of more effective treatments. My specific goals are to: 1) identify mechanisms mediating circadian gene effects on drug- and mood-related behaviors, and 2) identify how altering specific brain activity can alter alcohol-related behaviors and identify transcriptional mechanisms that underlie lasting reductions in binge-like drinking.
I am currently using several complementary approaches in mice to carry out the above research goals: a) clinically relevant drug self-administration models (operant drug self-administration and binge-drinking paradigms), b) viral-mediated gene transfer to temporally and spatially control gene expression and neuronal activity (using DesignerReceptors Exclusively Activated by Designer Drugs, DREADDs), c) behavioral battery of drug and mood-related assays, and d) identification of transcriptional mechanisms and the regulation of gene expression using RNA and ChIP Seq, qPCR, and Western blotting.Read more
Areas of interest
- Circadian gene regulation of mood- and alcohol-use disorders
- Testing and characterizing therapies for reducing alcohol and drug intake in animal models
- Ph.D., University of Texas, Austin Texas United States 2009
Pharmacogenetic Manipulation of the Nucleus Accumbens Alters Binge-Like Alcohol Drinking in Mice.Purohit K, Parekh PK, Kern J, Logan RW, Liu Z, Huang Y, McClung CA, Crabbe JC, Ozburn AR.Alcohol Clin Exp Res. 2018 May;42(5):879-888. doi: 10.1111/acer.13626. Epub 2018 Apr 18.PMID: 29668112.
Genome-Wide Expression Profiles Drive Discovery of Novel Compounds that Reduce Binge Drinking in Mice.Ferguson LB, Ozburn AR, Ponomarev I, Metten P, Reilly M, Crabbe JC, Harris RA, Mayfield RD.Neuropsychopharmacology. 2018 May;43(6):1257-1266. doi: 10.1038/npp.2017.301. Epub 2017 Dec 18.PMID: 29251283.
NPAS2 Regulation of Anxiety-Like Behavior and GABAA Receptors.Ozburn AR, Kern J, Parekh PK, Logan RW, Liu Z, Falcon E, Becker-Krail D, Purohit K, Edgar NM, Huang Y, McClung CA.Front Mol Neurosci. 2017 Nov 3;10:360. doi: 10.3389/fnmol.2017.00360. eCollection 2017.PMID: 29163035.
High Drinking in the Dark (HDID) mice are sensitive to the effects of some clinically relevant drugs to reduce binge-like drinking.Crabbe JC, Ozburn AR, Metten P, Barkley-Levenson A, Schlumbohm JP, Spence SE, Hack WR, Huang LC.Pharmacol Biochem Behav. 2017 Sep;160:55-62. doi: 10.1016/j.pbb.2017.08.002. Epub 2017 Aug 5.PMID: 28827047.
Functional Implications of the CLOCK 3111T/C Single-Nucleotide Polymorphism.Ozburn AR, Purohit K, Parekh PK, Kaplan GN, Falcon E, Mukherjee S, Cates HM, McClung CA.Front Psychiatry. 2016 Apr 21;7:67. doi: 10.3389/fpsyt.2016.00067. eCollection 2016.PMID: 27148095.
Commonalities and Distinctions Among Mechanisms of Addiction to Alcohol and Other Drugs.Ozburn AR, Janowsky AJ, Crabbe JC.Alcohol Clin Exp Res. 2015 Oct;39(10):1863-77. doi: 10.1111/acer.12810. Review.PMID: 26431116.
Circadian clock genes: effects on dopamine, reward and addiction.Parekh PK, Ozburn AR, McClung CA.Alcohol. 2015 Jun;49(4):341-9. doi: 10.1016/j.alcohol.2014.09.034. Epub 2015 Jan 8. Review.PMID: 25641765.
Direct regulation of diurnal Drd3 expression and cocaine reward by NPAS2.Ozburn AR, Falcon E, Twaddle A, Nugent AL, Gillman AG, Spencer SM, Arey RN, Mukherjee S, Lyons-Weiler J, Self DW, McClung CA.Biol Psychiatry. 2015 Mar 1;77(5):425-433. doi: 10.1016/j.biopsych.2014.07.030. Epub 2014 Aug 13.PMID: 25444159.
Differential regulation of the period genes in striatal regions following cocaine exposure.Falcon E, Ozburn A, Mukherjee S, Roybal K, McClung CA.PLoS One. 2013 Jun 11;8(6):e66438. doi: 10.1371/journal.pone.0066438. Print 2013.PMID: 23776671.
The role of clock in ethanol-related behaviors.Ozburn AR, Falcon E, Mukherjee S, Gillman A, Arey R, Spencer S, McClung CA.Neuropsychopharmacology. 2013 Nov;38(12):2393-400. doi: 10.1038/npp.2013.138. Epub 2013 May 31.PMID: 23722243.