Additional Contact Information:
Department of Biomedical Sciences
James H. Quillen College of Medicine
PO Box 70582
Johnson City, TN 37614
Office: Room 1-36 Bldg 1
Laboratory: Room 1-36 Bldg 119
Phone: (423) 439-8523
FAX: (423) 439-2017
Russell Brown, Ph.D.
James H. Quillen College of Medicine
East Tennessee State University
Department of Biomedical Sciences
Central Receiving, #1 CR Dr.
Johnson City, TN 37614
BS 1998 University of Oklahoma (Psychology and Chemistry)
MS 1995, PhD 1998 University of Kentucky (Experimental Psychology)
Postdoctoral Fellowship 1998-2000 University of Lethbridge, Lethbridge, Alberta, Canada (in the labs of Drs. Bryan Kolb and Ian Whishaw)
I am a behavioral neuroscientist, with a strong emphasis in psychopharmacology. My
research background actually began in the cognitive arena, analyzing underlying mechanisms
of behavioral ecological mechanisms in Dr. Lynn Devenport's lab at the University
of Oklahoma. This work continued in the laboratories of Dr. Phil Kraemer and Dr. Stephen
Scheff at the University of Kentucky studying ontogeny of learning and memory and
rodents, timing behavior in avians, as well as pharmacological approaches to improve
compensation after traumatic brain injury. I have always had a strong research interest
in brain plasticity and its response to experience.
At the end of my graduate school career, we began to analyze the effects of nicotine on cognitive function and in a rodent model of traumatic brain injury. I carried on this work in the laboratories of Drs. Bryan Kolb and Ian Whishaw at the University of Lethbridge, expanding my interests into the effects of nicotine on brain plasticity and compensation after brain injury.
I took a faculty position at East Tennessee State University (ETSU) in August of 2000, and through a collaboration, began pursuing mechanisms of psychostimulant addiction using a model of dopamine D2 receptor supersensitivity that originated in Dr. Rich Kostrzewa's lab in the Department of Pharmacology in Quillen College of Medicine at ETSU. Although Richs interests were more directed towards Parkinsons Disease and neurotoxicity, I realized this model had potential as a model of schizophrenia. From that point on, a major research focus in our lab centered on comorbidity in behavioral disorders, especially substance abuse in schizophrenia using the neonatal quinpirole model.
- Substance abuse comorbidity in behavioral disorders
- Sex differences in the response to psychostimulants
- The consequences of drug treatment on neural plasticity
1.Substance abuse comorbidity in Schizophrenia: In this line of research, our laboratory has analyzed the behavioral and neurochemical consequences of dopamine D2-like supersensitization. The dopamine D2 receptor is increased in its sensitivity through neonatal quinpirole (a dopamine D2/D3 agonist) treatment during the first three weeks of life in a rat. This increase in sensitivity does not result in a change in receptor number, and persists throughout the animals lifetime. Over several years of work, we have found that neonatal quinpirole treatment enhances behavioral sensitization and rewarding effects of nicotine. This is especially important because approximately 80% of schizophrenics smoke cigarettes, and they smoke heavily. Ultimately, this results in a poor quality of life and shortens the average lifespan in a smoking schizophrenic. Our primary interest here is to try to identify behavioral and neurobiological targets for treating smoking in schizophrenia.
2. Investigation of PARP inhibitors in Major Depressive Disorder. More recently, we
have begn one of two new research lines in my laboratory. One is a collaboration with
Dr. Greg Ordway, a faculty member in our department, analyzing novel pharmacological
targets for the treatment of Major Depressive Disorder. Dr. Ordway discovered an elevation
of the DNA repair enzyme Poly (ADP-ribose) polymerase (PARP) in the white matter of
human brain tissue of individuals that had suffered from major depression. We have
been investigating the effects of PARP inhibitors in preclinical rodent models of
depression with success. We believe we may have found a novel target for the treatment
of depression, and especially focusing this work towards individuals who are treatment-resistant
to current antidepressant treatments.
3. Novel anti-inflammatories for treatment of Alzheimer’s Disease. A third line of research is in collaboration with P2D Bioscience, Inc. (Cincinnati, OH) and Dr. Prasad Gabbita. We have been investigating the effects of several anti-neuroinflammatory drugs, given through the diet, to the 3xTg Alzheimer’s Disease model in the mouse. We have also had a considerable amount of success on this work, and hope to continue to do more research in the future.
Loren Peeters (BA, Tusculum College, 2019). Loren is finishing her first year in my
lab and has been involved in several projects thus far. She will likely pursue her
dissertation on the neonatal quinpirole model, and has some ideas as to where we may
go with these projects.
Liza Hernandez (BA, ETSU, 2015). Liza rejoined the lab after completing her Master’s Degree in the Department of Psychology at ETSU. Liza’s dissertation will likely focus on the Depression model in collaboration with Dr. Ordway.
Recent graduate: Drew Gill (BS Davidson College 2015; PhD ETSU 2020). Drew defended his dissertation in the middle of the COVID-19 pandemic, and is headed to a postdoctoral fellowship with the Food & Drug Administration in Little Rock, AR. Drew worked hard in our laboratory and we wish him the best!
ACTIVE RESEARCH FUNDING:
1 R15 DA04926-01
Brown, Russell W. (PI) 04/01/19-03/31/22
“The role of adenosine A(2A) receptor activation on the behavioral and plasticity response to nicotine in a rodent model of schizophrenia.” This project is designed to analyze the role of adenosine A(2A) receptor as a target for reducing the rewarding aspects of nicotine in a rodent model of schizophrenia developed in our laboratory.
Role: Principal Investigator
Subaward to NIH SBIR SB1: 5R44 AG051302-03
Gabbita, S. Prasad (PI) 08/01/18 – 07/31/20
“Application of novel anti-inflammatory drugs towards Alzheimer’s Disease.”
This project is designed to analyze novel TNF-alpha modulators towards alleviating behavioral and neurobiological deficits in the 3xTg Alzheimer’s Disease model in the mouse.
Zhu, Meng-Yang (PI) 10/01/18-09/30/21
“Restoration of noradrengergic and dopaminergic functions in the brain of aged rats.”
This project is designed to analyze genetic alterations in the noradrenergic system and its effects on stress-related behaviors. Our laboratory’s role is in stress behavioral testing.
Chandley, Michelle J. (PI) 05/01/19-04/30/22
“Neuroinflammatory mediators of glutamatergic and gabaergic neuropathology in the anterior cingulate cortex of Autism Spectrum Disorder.” This project is designed to analyze neuropathology in both human post-mortem brain tissue and in an animal model of autism. Our role is to help with social interaction behavioral testing.
Gill WD, Shelton HW, Burgess KC, Brown RW. Effects of an adenosine A(2A)
agonist on the rewarding associative properties of nicotine and neural plasticity
in a rodent model of schizophrenia. J Psychopharmacol. 2020 Jan;34(1):137-144.
Allen SA, Tran LH, Oakes HV, Brown RW, Pond BB. Dopaminergic Effects of Major Bath
Salt Constituents 3,4-Methylenedioxypyrovalerone (MDPV), Mephedrone, andMethylone
Are Enhanced Following Co-exposure. Neurotox Res. 2019Jul;36(1):132-143. PMID: 30879275.
Jia C, Brown RW, Malone HM, Burgess KC, Gill WD, Keasey MP, Hagg T. Ciliaryneurotrophic factor is a key sex-specific regulator of depressive-like behaviorin mice. Psychoneuroendocrinology. 2019 Feb;100:96-105. PMID: 30299260
Kostrzewa RM, Wydra K, Filip M, Crawford CA, McDougall SA, Brown RW,Borroto-Escuela
DO, Fuxe K, Gainetdinov RR. Dopamine D(2) ReceptorSupersensitivity as a Spectrum of
Neurotoxicity and Status in PsychiatricDisorders. J Pharmacol Exp Ther. 2018 Sep;366(3):519-526.
Brown RW, Schlitt MA, Owens AS, DePreter CC, Cummins ED, Kirby SL, Gill WD,Burgess KC. Effects of Environmental Enrichment on Nicotine Sensitization in RatsNeonatally Treated with Quinpirole: Analyses of Glial Cell Line-DerivedNeurotrophic Factor and Implications towards Schizophrenia. Dev Neurosci.2018;40(1):64-72. PMID:29444518. Ordway GA, Szebeni A, Hernandez LJ, Crawford JD, Szebeni K, Chandley MJ,Burgess KC, Miller C, Bakkalbasi E, Brown RW. Antidepressant-Like Actions ofInhibitors of Poly(ADP-Ribose) Polymerase in Rodent Models. Int JNeuropsychopharmacol. 2017 Dec 1;20(12):994-1004. doi: 10.1093/ijnp/pyx068.PubMed PMID: 29016792; PubMed Central PMCID: PMC5716178.
Szebeni A, Szebeni K, DiPeri TP, Johnson LA, Stockmeier CA, Crawford JD, Chandley
MJ, Hernandez LJ, Burgess KC, Brown RW, Ordway GA. (2017). Elevated DNA Oxidation
and DNA Repair Enzyme Expression in Brain White Matter in Major Depressive Disorder.
International Journal of Neuropsychopharmacology. 20(5):363-373. PMID: 28034960.
Cummins ED, Leedy KK, Dose JM, Peterson DJ, Kirby SL, Hernandez LJ, Brown RW. (2017). The effects of adolescent methylphenidate exposure on the behavioral and brain-derived neurotrophic factor response to nicotine. Journal of Psychopharmacology. 31(1):75-85. PMID: 27940499
Kostrzewa RM, Nowak P, Brus R, Brown RW. (2016). Perinatal Treatments with the Dopamine D-Receptor Agonist Quinpirole Produces Permanent D-Receptor Supersensitization: a Model of Schizophrenia. Neurochemical Research. 41(1-2):183-92. PMID: 26547196.
Danysz, W., Fink, G., McCreary, A., Tober, C., Dimpfel, W., Bizot, J. C., Kostrzewa, R. M., Brown, R. W., Jetzke, C. C., Greco, S., Jensen, A. K., Parsons, C. G. (2015). Effects of sarizotan in animal models of ADHD challenging PK-PD relationship. Journal of Neural Transmission Mar 22 Epub ahead of print. PMID:25796190