David A. Baker, Ph.D.

B.S., 1992, Montana State University

Ph.D., 1999, Arizona State University

Postdoctoral Fellow, Medical University of South Carolina

Schroeder Health Complex, 405

(414) 288-6638 or 288-6635

E-mail

Probing Outside of the Synapse: Contribution of Extrasynaptic Glutamate to Neuropsychiatric Disorders

Glutamate represents the primary excitatory neurotransmitter and is involved in most aspects of brain functioning in the normal and diseased states.  While synaptically released glutamate has been studied in great detail, a dearth of knowledge exists regarding the contribution of extrasynaptic glutamate release mechanisms, including cystine-glutamate antiporters, to pathological conditions involving glutamate dysfunction.  Of particular interest is the contribution of nonvesicular glutamate release from cystine-glutamate antiporters to the pathophysiological state produced by repeated cocaine administration to study drug addiction or the NMDA antagonist phencyclidine to study schizophrenia.  The goal of my research is to determine whether extrasynaptic release mechanisms represent unrecognized targets in unmasking the etiology and treatment of psychiatric disorders, namely schizophrenia and cocaine addiction.  

We utilize a pathophysiological approach whereby the involvement of extrasynaptic release mechanisms in neuropsychiatric disorders is examined using preclinical models of schizophrenia and cocaine addiction.  Towards this end, the laboratory incorporates a number of molecular, cellular, and behavioral techniques to address these questions.  Funding for these endeavors is provided by grants from the National Institute on Drug Abuse, National Institute of Mental Health, the Biomedical Technology Alliance, and the National Alliance for Research on Schizophrenia and Depression.

Selected References:

1. Neisewander, J.L., Baker, D.A., Fuchs, R.A., Tran-Nguyen, L.T.L., Palmer, A., Marshall, J.F. (2000) Fos protein expression and cocaine-seeking behavior in rats after exposure to a cocaine self-administration environment. Journal of Neuroscience, 15, 798-805.

2. Swanson, C.J., Baker, D.A., Carson, D., Worley, P.F., Kalivas, P.W. (2001) Repeated cocaine administration attenuates group I metabotropic glutamate receptor-mediated glutamate release and behavioral activation: A potential role for Homer1bc. Journal of Neuroscience, 21, 9043-9052.

3. Baker, D.A., Tran-Nguyen, L.T.L., Fuchs, R.A., and Neisewander, J.L. (2001) Differential effects of chronic fluoxetine treatment on cocaine-seeking behavior elicited by a cocaine or a cocaine environment. Psychopharmacology, 155, 18-26.
4. Xi, Z.X., Baker, D.A., Shen, H., Carson, D.S. & Kalivas, P.W. (2002) Group II metabotropic glutamate receptors modulate extracellular glutamate in the nucleus accumbens. Journal of Pharmacology and Experimental Therapeutics, 300, 162-171.
5. Xi, Z.X., Ramamoorthy, S., Baker, D.A., Shen, H., Samuvel, D.J., Kalivas, P.W. (2002) Modulation of group II metabotropic glutamate receptor signaling by chronic cocaine. Journal of Pharmacology and Experimental Therapeutics, 303, 608-615.
6. Baker, D.A., Xi, Z.X., Shen H., Swanson C.J., & Kalivas, P.W. (2002) The primary source and neuronal function of in vivo non-synaptic glutamate. Journal of Neuroscience, 22, 9134-9141.
7. Xi, Z.X., Shen, H., Baker, D.A., & Kalivas, P.W. (2003) Inhibition of non-vesicular glutamate release by group III metabotropic glutamate receptors in the nucleus accumbens. Journal of Neurochemistry, 87, 1204-12.
8. Baker, D.A., McFarland, K., Lake, R.W., Shen, H., Toda, S., Kalivas, P.W. (2003) Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse. Nature Neuroscience, 6, 743-749.