Neurosciences : Bryan Yamamoto, Ph.D.

Office: Block Health Sciences Building, Room 130B         

Email:  Bryan.Yamamoto@utoledo.edu

B.A., 1975, UCLA
MA.  1977, California State University
PhD., 1981, Syracuse University 

Our primary research interests are in neuropharmacology, neurodegeneration, and the neurotoxicity of the amphetamines, in particular, methamphetamine (Speed) and MDMA (Ecstasy). The overall hypothesis is that the amphetamines, through the enhanced release of dopamine and glutamate, promote excitotoxicity, free-radical mediated oxidative stress, and produce a compromised bioenergetic state that damage dopamine and 5HT neurons.  We have been continuously funded by the NIH since 1986.

The methodologies used in our lab range from environmental manipulations and measures of behavior to cellular approaches such as in vivo microdialysis, cell culture, immunohistochemistry, protein biochemistry, and measures of oxygen free radicals and oxidative stress.    

Cellular mechanisms of MDMA and METH toxicity

Cultures of 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 tyrosine-induced dopamine formation in neurons and the role of abnormal protein degradation in causing cell death.

METH toxicity – role of glutamate and oxidative stress

We have a long-standing interest in the mechanisms mediating the toxicity of the widely abused psychostimulant drug, methamphetamine.  Methamphetamine (METH) damages dopamine and serotonin nerve terminals but the exact mechanisms leading to this damage are unknown.  We are evaluating the causes and consequences of METH toxicity using approaches that span cellular to behavioral methods.  Possible mechanisms that are being examined include impairments of the mitochondrial electron transport chain, glutam ate derived reactive oxygen species, activation of calcium-dependent intracellular proteins, and measures of cell death in select brain regions involved in movement.  An animal model is currently being established to assess the functional consequences of damage to cells in the motor output pathway of the extrapyramidal motor system.

Stress and Vulnerability to Methamphetamine and Ecstasy Toxicity

Environmental stress and drug abuse are inextricably linked.  We are examining how chronic psychological stress can 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.

 Drugs of Abuse and the Blood-Brain-Barrier


Studies are underway to examine how stimulant drugs of abuse alter the permeability of the blood-brain barrier to damage 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.

Eyerman, D and Yamamoto, B.K.  Lobeline attenuates methamphetamine induced changes in VMAT-2 immunoreactivity and monoamine depletions in the striatum.  J. Pharmacology and Experimental Therapeutics 312: 160-169, 2005.

Darvesh A. S., Yamamoto B. K. and Gudelsky, G. A.  Evidence for the involvement of nitric oxide in 3,4-methylenedioxymethamphetamine-induced serotonin depletion in the rat brain.  J. Pharmacology and Experimental Therapeutics 312: 694-701, 2005.

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.

Staszewski, R.D. and Yamamoto, B.K.  Methamphetamine-induced spectrin proteolysis in the rat striatum.  J. Neurochemistry 96: 1267-1276, 2006.

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.

Hatzipetros, T and Yamamoto, B.K.  Dopaminergic and GABAergic Modulation of Glutamate Release from Rat Subthalamic Nucleus Efferents to the Substantia Nigra.  Brain Research, 1076: 60-67, 2006.

Quinton, M.S. and Yamamoto, B.K.  Causes and Consequences of Methamphetamine and MDMA Toxicity.  Am. Association of Pharmaceutical Sciences Journal 8: E337-E347, 2006.

Cunningham, J.I. and Yamamoto, B.K.  Interactions Between Stress and MDMA:  Implications for Neurotoxicity.  Cell Science Reviews 3:  198-221, 2006.

Yamamoto, B.K. and Bankson, M.G.  Amphetamine Neurotoxicity:  Cause and Consequence of Oxidative Stress.  Critical Reviews in Neurobiology 17:  87-117, 2005.

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.

Raudensky, J. and Yamamoto, B.K.  Effects of chronic unpredictable stress and methamphetamine on hippocampal glutamate function.  Brain Research 1135:129-35, 2006.

Raudensky, J. and Yamamoto, B.K.  Effects of chronic unpredictable stress on monoamine transporter immunoreactivity and methamphetamine-induced dopamine release in the nucleus accumbens shell.  Synapse 61: 353-355, 2007.

Broom, S.L. and Yamamoto.  Role of Norepinephrine in Substance Abuse.  In:  Brain Norepinephrine: Neurobiology and Therapeutics, eds. Gregory Ordway, Michael Schwartz and Alan Frazer. Cambridge University Press; Cambridge, UK, 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.