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| Neuroscience
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Mark Thomas, Ph.D.
Assistant Professor, Department of Neuroscience
tmhomas@umn.edu |
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 Neurobiology
of drug-induced plasticity and addiction.
A fundamental question in neuroscience is how the structure and function
of the brain is modified by experience. One compelling model of experience-dependent
plasticity is behavioral sensitization—a long-lasting increase in
the locomotor stimulatory effects of drugs of abuse following repeated
exposure. Behavioral sensitization is also a prominent model for
the intensification of drug craving that occurs in human addicts.
My laboratory seeks to identify the cellular and molecular mechanisms
that underlie this form of plasticity, as well as the genetic factors
that may predispose an individual to sensitization. We are currently
studying two cellular correlates of drug-induced plasticity, long-term
depression at glutamatergic synapses in the nucleus accumbens—a key
site of action of drugs of abuse in the brain—and the increases in
the length of dendrites and the density of dendritic spines that also
occur in accumbens neurons. We are using several complementary approaches
to determine the relationship that each of these correlates has with
behavioral sensitization and with each other: behavioral studies
to determine the consequences of drug exposure, the use of transgenic
and knockout mice, analysis of dendritic morphology via several staining
methods and whole-cell recordings in brain slices to investigate synaptic
function. These studies will provide insight into the cellular and
molecular mechanisms of an important form of experience-dependent
plasticity that may hold some of the clues to drug addiction. |
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Selected Publications
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Ferguson SM, Thomas MJ and Robinson TE. (2004)“Morphine-induced c- fos mRNA expression in striatofugal circuits: modulation by dose, environmental context and drug history.” Neuropsychopharmacology, 29:1664-1674. |
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Dong Y, Saal D, Thomas MJ , Faust R, Bonci A, Robinson TE and Malenka RC. (2004) “Cocaine-induced potentiation of synaptic strength in dopamine neurons: behavioral correlates in GluRA(-/-) mice.” Proceedings of the National Academy of Sciences of the United States of America, 101:14282-14287. |
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Thomas, M.J. and Malenka, R.C.
Synaptic plasticity in the mesolimbic dopamine system.
Philosophical Transactions of the Royal Society of London B 2003 358:815-819 |
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Thomas, M.J., Beurrier, C., Bonci, A., and Malenka, R.C.
Long-term depression in the nucleus accumbens: A neural correlate of behavioral sensitization to cocaine.
Nature Neuroscience 2001 4(12):1217-23 |
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Thomas, M.J., Malenka, R.C., and Bonci, A.
Modulation of long-term depression by dopamine in the mesolimbic system.
Journal of Neuroscience 2000 20:5581-5586 |
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