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| Neuroscience
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Mark Thomas, Ph.D.
Associate 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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Rothwell P.E., Thomas M.J. and Gewirtz J.C. (2011)
Protracted manifestations of acute dependence after a single morphine exposure.
Psychopharmacology (Berl). Aug. 11, 2011 [Epub ahead of print] |
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Rothwell P.E., Kourrich S. and Thomas M.J. (2011)
Synaptic adaptations in the nucleus accumbens caused by experiences linked to relapse.
Biol. Psychiatry. 69(11): 1124-26 |
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Rothwell P.E., Kourrich S. and Thomas M.J. (2011)
Environmental novelty causes stress-like adaptations at nucleus accumbens synapses: implications for studying addiction-related plasticity.
Neuropharmacology 61(7): 1152-59 |
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Rothwell P.E., Gewirtz J.C. and Thomas M.J. (2010)
Episodic withdrawal promotes psychomotor sensitization to morphine.
Neuropsychopharmacology 35(13): 2579-89 |
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Xie K., Allen K.L., Kourrich S., Colón-Saez J., Thomas M.J., Wickman K. and Martemyanov K.A. (2010)
Gbeta5 recruits R7 RGS proteins to GIRK channels to regulate the timing of neuronal inhibitory signaling.
Nat. Neurosci. 13(6): 661-63 |
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Anderson G.R., Cao Y., Davidson S., Truong H.V., Pravetoni M., Thomas M.J., Wickman K., Giesler G.J. Jr and Martemyanov K.A. (2010)
R7BP complexes with RGS9-2 and RGS7 in the striatum differentially control motor learning and locomotor responses to cocaine.
Neuropsychopharmacology 35(4): 1040-50 |
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Petzold A.M., Balciunas D., Sivasubbu S., Clark K.J., Bedell V.M., Westcot S.E., Myers S.R., Moulder G.L., Thomas M.J. and Ekker S.C. (2009)
Nicotine response genetics in the zebrafish.
Proc. Natl. Acad. Sci. USA. 106(44): 18662-67 |
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Kourrich S. and Thomas M.J. (2009)
Similar neurons, opposite adaptations: psychostimulant experience differentially alters firing properties in accumbens core versus shell.
J. Neurosci. 29(39): 12275-83 |
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Sun M., Thomas M.J., Herder R., Bofenkamp M.L., Selleck S.B. and O'Connor M.B. (2009)
Distinct profiles of anxiety and dysphoria during spontaneous withdrawal from acute morphine exposure.
Neuropsychopharmacology 34(10): 2285-95 |
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Sun M., Thomas M.J., Herder R., Bofenkamp M.L., Selleck S.B. and O'Connor M.B. (2007)
Cocaine experience controls bidirectional synaptic plasticity in the nucleus accumbens.
J. Neurosci. 27(30): 7921-28 |
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Sun M., Thomas M.J., Herder R., Bofenkamp M.L., Selleck S.B. and O'Connor M.B. (2007)
Presynaptic contributions of chordin to hippocampal plasticity and spatial learning.
J. Neurosci. 27(29): 7740-50 |
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Ferguson S.M., Thomas M.J. and Robinson T.E. (2004)
Morphine-induced c- fos mRNA expression in striatofugal circuits: modulation by dose, environmental context and drug history.
Neuropsychopharmacology 29: 1664-74 |
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Dong Y., Saal D., Thomas M.J., Faust R., Bonci A., Robinson T.E. and Malenka R.C. (2004)
Cocaine-induced potentiation of synaptic strength in dopamine neurons: behavioral correlates in GluRA(-/-) mice.
Proc. Natl. Acad. Sci. USA, 101(39): 14282-87 |
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Thomas M.J. and Malenka R.C. (2003)
Synaptic plasticity in the mesolimbic dopamine system.
Philos. Trans. R. Soc. Lond. B Biol. Sci. 358(1432): 815-19 |
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Thomas M.J., Beurrier C., Bonci A. and Malenka R.C. (2001)
Long-term depression in the nucleus accumbens: A neural correlate of behavioral sensitization to cocaine.
Nat. Neurosci. 4(12): 1217-23 |
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Thomas M.J., Malenka R.C. and Bonci, A. (2000)
Modulation of long-term depression by dopamine in the mesolimbic system.
J. Neurosci. 20: 5581-86 |
Lab Website
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