The Laboratory of
Neurochemistry is under the direction of Bryan K. Yamamoto, Ph.D. (bkyam@bu.edu).
Our research interests are focused on 5 different but related areas of
investigation.
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A primary interest is in the mechanisms underlying
the neurotoxicity of methamphetamine and MDMA (“Ecstasy, “E”,).
We are studying how mitochondrial dysfunction, oxidative stress,
and excitotoxicity contribute to the long-term neurotoxic effects of substituted
amphetamines on brain dopamine and serotonin systems.
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Another interest is in the functional consequences
of exposure to methamphetamine and MDMA. Since methamphetamine and MDMA deplete
the brain of dopamine and/or serotonin, behaviors related to movement and
psychiatric disorders including depression and drug abuse, as well as sleep
and other physiological functions, are being examined using rat models.
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There are ongoing research projects aimed at understanding
the interactions between chronic stress and the vulnerability to amphetamine
neurotoxicity. We are examining how prior exposure to either chronic
stress or amphetamines can affect the responses of the brain to a subsequent
exposure to amphetamines or acute stress, respectively. The hypotheses being tested are that
prior exposure to stress enhances the vulnerability of the brain to the
neurotoxic effects of the amphetamines. Conversely, prior administration of neurotoxic doses of
amphetamines enhances the deleterious effects of a subsequent exposure to
an acute stressor.
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The mesolimbic dopamine system is important in mediating
the neurobehavioral effects drugs of abuse. We are interested in how serotonin,
GABA and glutamate interact to modulate this system and how these interactions
are affected by psychostimulants.
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A long-standing research interest of our lab has
been in the neurochemical regulation of basal ganglia function. Current research efforts are directed
at understanding the regulation of the outflow of the basal ganglia, namely,
the control of the substantia nigra by the subthalamic nucleus as well as
the regulation of the thalamus by the basal ganglia.
These studies have implications for the control of movement under
normal and pathological conditions (e.g. Parkinson’s disease).
We
use both in vivo and in vitro methods. The methodologies
we employ range from environmental manipulations of behavior to cellular approaches
such as in vivo microdialysis,
immunohistochemistry, protein biochemistry, and assays of oxygen free radicals
and oxidative stress.