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Bryan Yamamoto, PhD

Robert Forney Professor of Toxicology
Chair, Department of Pharmacology & Toxicology

 EDUCATION

1975  

B.A. | Psychobiology | UCLA | Los Angeles, CA

1977

M.A. | Experimental Psychology | California State University, Fullerton, CA

1981

Ph.D. |  Neurobiology | Syracuse University Syracuse, NY

1985

Postdoctoral Fellow| Clinical Pharmacology, University of Colorado School of Medicine, Denver, CO

 

 HONORS 

 

 

Phi Kappa Phi National Honor Society

1997

NARSAD Independent Investigator Award

2008

Raymond and Beverly Sackler Distinguished Professor of Neurosciences | University of Toledo Health Sciences Center

1993-1997  

NIH Study Section Regular Member

1999-2003

NIH Study Section Regular Member

2008-2012

NIH Study Section Regular Member

2007-2010

NIH/NINDS Program Advisory Committee for the Specialized Neuroscience Research Program (SNRP) at Hunter College

2009-present

Scientific Advisory Board-NIDA sponsored Methamphetamine Research Center, Oregon Health and Science University, Portland, Oregon

2010-present

Scientific Advisory Board to Translational Methamphetamine AIDS Research Center at the University of California, San Diego

2010-present

Scientific Advisory Board - R24 Diversity Drug Abuse Research Program (DIDARP)-University of Hawaii

2015-present       

Robert B. Forney Professor of Toxicology

 

 

 

 

METH and MDMA Neurotoxicity – role of glutamate, oxidative stress, and neuroinflammation

We have a long-standing interest in the mechanisms mediating the toxicity of the widely abused psychostimulant drugs, methamphetamine and MDMA.  Methamphetamine (METH) and MDMA damage dopamine and/or serotonin nerve terminals but the exact mechanisms leading to this damage are unknown.  

We are evaluating the causes and consequences of METH and MDMA toxicity using approaches that span cellular to behavioral methods.  Possible mechanisms that are being examined include impairments of the mitochondrial electron transport chain, glutamate derived reactive oxygen species, activation of calcium-dependent intracellular proteins, neuroinflammation, and measures of cell death in select brain regions involved in movement and cognition.  

Cellular mechanisms of MDMA and METH toxicity 

Cultures of serotonin neurons are being used to examine the mechanisms mediating the toxic actions of the amphetamines.  Measures of oxidative stress using traditional and novel assays, cell morphology, mitochondrial function and transporter protein trafficking are being examined.  We are also examining the effects of dopamine formation in serotonin neurons and the role of abnormal protein degradation in causing cell death.
 

 

Stress and Vulnerability to Methamphetamine and MDMA Toxicity

Environmental stress and drug abuse are inextricably linked.  We are examining how chronic psychological stress alone can produce long-term changes in serotonin transmission and alter 

the neurochemical, physiological, and behavioral consequences of the amphetamines.  Conversely, we also are conducting experiments that evaluate how prior exposure to the amphetamines can alter the neurochemical, neuroanatomical, and behavioral effects of chronic stress.  Various limbic and motor areas of the brain are being examined for their roles in the dangerous interplay between stress and amphetamines on learning/memory and anxiety. Chronic stress produces a loss of tryptophan positive neurons (Yellow) in the interfascicular nucleus of the dorsal raphe.

Drugs of Abuse and the Blood-Brain-Barrier

Studies are underway to examine how stimulant drugs of abuse interact with chronic stress to alter the permeability of the blood-brain barrier thereby damaging the brain’s natural defense against the invasion of toxins.  Anatomical and protein biochemical approaches are being used to assess the permeability of the blood brain barrier after drugs and stress. As shown, FITC dextran extravasation from capillaries is evident after METH.
 

 

Selected Publications

 
  • Mark, K.A., Soghomonian, J-J, Yamamoto, B.K. High-Dose Methamphetamine Acutely Activates the Striatonigral Pathway to Increase Striatal Glutamate and Mediate Long-term Dopamine Toxicity. Journal of Neuroscience 24: 11449-11456, 2004.
  • Broom, S.L. and Yamamoto, B.K.  Effects of Subchronic Methamphetamine Exposure on Basal DA and Stress-induced Dopamine Release in the Nucleus Accumbens Shell of Rats.  Psychopharmacology, 181:467-76, 2005.
  • Brown, J.M., Quinton, M.S. and Yamamoto, B.K.    Methamphetamine-Induced inhibition of mitochondrial complex II:  Roles of glutamate and peroxynitrite.  J. Neurochemistry 95: 429-436, 2005.
  • Breier, J.M., Bankson, M.G., and Yamamoto, B.K.  L-Tyrosine contributes to (+)-3,4-Methylenedioxymethamphetamine (MDMA)-induced serotonin depletions.  J. Neuroscience, 26: 290-299, 2006.
  • Amato, J.L. and Yamamoto, B.K.  Prior Exposure to Chronic Stress and MDMA Potentiates Mesoaccumbens Dopamine Release Mediated by the 5HT1B Receptor.  Neuropsychopharmacology, 32: 946–954, 2007.
  • Tata, D and Yamamoto, B.K.  Interactions between Methamphetamine and Psychological Stress: Role of Glutamate, Oxidative Stress and Mitochondrial Dysfunction.  Addiction, 102 (Suppl 1):  49-60, 2007.
  • Quinton, M.S. and Yamamoto, B.K.  Neurotoxic Effects of Chronic Stress in the Striatum of Methamphetamine-Exposed Rats.  Psychopharmacology 193:341-50, 2007.
  • Hatzipetrros, T., Raudensky, J., Soghomonion, J-J, and Yamamoto, B.K.  Haloperidol Treatment After High Dose Methamphetamine Administration is Excitotoxic to GABA Cells in the Substantia Nigra Pars Reticulata.  J. Neuroscience 27: 5895-5902, 2007.
  • Mark, K.A., Russek, S.J. and Yamamoto, B.K.  Dynamic Changes in Vesicular Glutamate Transporter (VGLUT1) Function and Expression Related to Methamphetamine-Induced Glutamate Release. J. Neuroscience 27: 6823-6831, 2007.
  • Tata, D, Raudensky, J, and Yamamoto, B.K.    Augmentation of Methamphetamine-induced Toxicity in the Striatum by Unpredictable Stress: Role of Hyperthermia.  European Journal of Neuroscience 26: 739-748, 2007.
  • Eyerman, D.J. and Yamamoto, B.K.  A Rapid Oxidation and Persistent Decrease in the Vesicular Monoamine Transporter 2 after Methamphetamine, J. Neurochemistry  103: 1219-1227, 2007.
  • Tata, D. and Yamamoto, B.K.  Chronic Stress Enhances Methamphetamine-Induced Extracellular Glutamate and Excitotoxicity in the Rat Striatum, Synapse 62:325-336, 2008.
  • Gudelsky G.A and Yamamoto, B.K.  Actions of 3,4-Methylenedioxymethamphetamine (MDMA) on Cerebral Dopaminergic, Serotonergic and Cholinergic Neurons.  Pharmacology, Biochemistry, and Behavior, 90: 198-207, 2008.
  • Yamamoto, B.K. and Raudensky J. The Role of Oxidative Stress, Metabolic Compromise, and Inflammation in Neuronal Injury Produced by Amphetamine-Related Drugs of Abuse. J. Neuroimmune Pharmacology, 3: 203-217, 2008. PMID: 18709468
  • Johnson, B.N. and Yamamoto, B.K. Chronic Unpredictable Stress Augments +3,4-Methylenedioxymethamphetamine (MDMA)-induced Monoamine Depletions: The Role of Corticosterone. Neuroscience 159 1233–1243, 2009.
  • Cunningham, J, Raudensky, J, Tonkiss, J, and Yamamoto, B.K. MDMA Pretreatment Leads to Mild Chronic Unpredictable Stress-induced Impairments in Spatial learning. Behavioral Neuroscience, 123:1076-84, 2009.
  • Doyle, J.R. and Yamamoto, B.K. Serotonin 2 receptor modulation of hyperthermia, corticosterone, and hippocampal serotonin depletions following serial exposure to chronic stress and methamphetamine. Psychoneuroendocrinology 35: 629-622, 2010 PMID 19879056
  • Northrop, N.A. and Yamamoto, B.K. Neuroimmune Pharmacology from a Neuroscience Perspective. Journal of Neuroimmune Pharmacology, 6: 10-19, 2011. PMID 20717737
  • Northrop, N.A., Smith, L.P., Yamamoto, B.K. and Eyerman, D.J. Regulation of Glutamate Release by Alpha 7 Nicotinic Receptors: Differential Role in Methamphetamine-Induced Damage to Dopaminergic and Serotonergic Terminals. Journal of Pharmacology and Experimental Therapeutics 336: 900-907, 2011. PMID 21159748
  • Moszczynska, A. and Yamamoto, B.K. Methamphetamine oxidatively damages parkin and decreases the activity of 26S proteasome in vivo. Journal of Neurochemistry, 116: 1005-1017, 2011. PMID: 21166679
  • Natarajan, R. and Yamamoto, B.K. The Basal Ganglia as a Substrate for the Multiple Actions of Amphetamines. Basal Ganglia 1: 49-57, 2011. PMID 21804952
  • Northrop, N and Yamamoto, B.K. Persistent Neuroinflammatory Effects of Serial Exposure to Chronic Stress and Methamphetamine on the Blood Brain Barrier, Journal of Neuroimmune Pharmacology 7: 951-968, 2012
  • Halpin, L. and Yamamoto, B.K. Peripheral ammonia as a mediator of methamphetamine neurotoxicity. Journal of Neuroscience 32(38):13155–13163, 2012. PMID: 22993432
  • Stansley, B.J. and Yamamoto, B.K. L-dopa-induced dopamine synthesis and oxidative stress in serotonergic cells. Neuropharmacology 67: 243-251, 2013.
  • Anneken, J.H., Cunningham, J.I., Collins, S.A., Yamamoto, B.K. and Gudelsky, G.A. MDMA increases glutamate release and reduces parvalbumin-positive GABAergic cells in the dorsal hippocampus of the rat: role of cyclooxygenase. J. Neuroimmune Pharmacol. 8 :58-65, 2013.  PMID: 23179355
  • Northrop, N.A. and Yamamoto, B.K.  Cyclooxygenase activity contributes to the monoaminergic damage caused by serial exposure to stress and methamphetamine. Neuropharmacology 72: 96-105, 2013.  PMID: 23643743
  • Halpin, L.E., Gunning III, W.T.  and Yamamoto, B.K.  Methamphetamine Causes Acute Hyperthermia-Dependent Liver Damage.  Pharmacology and Research Perspectives, 1: 1-11, 2013.
  • Halpin, L.E. and Yamamoto, B.K.  Ammonia Mediates Methamphetamine-Induced Increases in Glutamate and Excitotoxicity.  Neuropsychopharmacology, 39: 1031-1038, 2014. PMID: 24165886
  • Halpin, L.E., Collins, S.A. and Yamamoto, B.K.  Neurotoxicity of Methamphetamine and 3,4-methylenedioxymethamphetamine.  Life Sciences, 97: 37-44, 2014. PMID: 23892199
  • Stansley, B. and Yamamoto, B.K.  Chronic L-dopa decreases serotonin neurons in a sub-region of the dorsal raphe nucleus, Journal of Pharmacology and Experimental Therapeutics, 351:440-447, 2014.  PMID 25212217
  • Poddar, N, Zano, S., Natarajan, R., Yamamoto B., and Viola, R.E.  Enhanced brain distribution of modified aspartoacylase.  Molecular Genetics and Metabolism 113: 219-224, 2014  PMID: 25066302
  • Northrop, N.A. and Yamamoto, B.K.  Methamphetamine neurotoxicity and neuroinflammatory processes.  In:  Neuroinflammation and Neurodegeneration, P.K. Peterson and M. Taborek, eds., Springer, pp. 443-462, 2014
  • Northrop, N.A. and Yamamoto, B.K.  Methamphetamine Effects on Blood-Brain Barrier Structure and Function, Frontiers in Neuroscience-Neuropharmacology, 9: 69, 2015. http://dx.doi.org/10.3389/fnins.2015.00069
  • Collins, S.A., Gudelsky, G.A. and Yamamoto, B.K.  MDMA-induced loss of parvalbumin interneurons within the dentate gyrus is mediated by 5HT2a and NMDA receptors.  Eur. J. Pharmacology, 761:95-100, 2015
 

Department of Pharmacology and Toxicology | 635 Barnhill Drive, MS A401 | Indianapolis, IN 46202