Neuropsychopharmacology: A Tribute to Joseph T. Coyle

Dr. Robert Schwarcz is Professor of Psychiatry, Pharmacology and Pediatrics, Director of the NIMH Conte Center for Translational Research, and Head of Neuroscience, Maryland Psychiatric Research Center, at the University of Maryland School of Medicine. After receiving his PhD degree in Biochemistry from the University of Vienna, Austria, he showed in the 1970s, under the mentorship of Dr. Coyle, that an intrastriatal injection of the excitatory amino acid kainate provides an animal model for Huntington's disease. This led to the idea that excitotoxic processes, triggered by an overstimulation of excitatory amino acid receptors, are causally involved in the pathophysiology of several major neurological diseases. As an offshoot of the excitotoxic hypothesis, Dr. Schwarcz developed the concept and demonstrated that antagonists of excitatory amino acid ("glutamate") receptors prevent or arrest neurodegeneration and hold promise as novel therapeutic agents for major brain diseases. This eventually led to the establishment of anti-excitotoxin-based drug discovery programs in a large number of pharmaceutical houses throughout the world. More recently, most of Dr. Schwarcz’ work has been concerned with the neurobiology of quinolinate (QUIN) and kynurenate (KYNA), two metabolically related brain constituents with neuroexcitatory (and excitotoxic) and neuroinhibitory (and neuroprotective) properties, respectively. Both QUIN and KYNA are products of the kynurenine pathway of tryptophan degradation. Using a combination of biochemical, histological, behavioral and electrophysiological techniques, he elaborated many of the characteristics and control mechanisms which govern the function of QUIN and KYNA in the brain. Ongoing in vivo and in vitro studies are designed 1) to identify possible abnormalities in kynurenine pathway metabolism in Huntington’s disease, schizophrenia and depression, and in relevant animal models; 2) to further define the neurobiology of QUIN and KYNA by manipulating the kynurenine pathway pharmacologically and genetically; and 3) to develop and use novel kynurenergic drugs in order to normalize functional impairments in the central nervous system. Dr. Schwarcz has published over 300 peer-reviewed manuscripts and received several major national and international awards and honors, including election as Foreign Professor of the Karolinska Institute in Stockholm in 2009.

Preface
Robert Schwarcz and S.J. Enna
Foreword
Solomon H. Snyder
1. My Life in Clinical Neuroscience: The Beginning
Joseph T Coyle
2. Kynurenines and Glutamate: Multiple Links and Therapeutic Implications
Robert Schwarcz
3. The Therapeutic Role of D-Cycloserine in Schizophrenia
Donald Goff
4. Impulsivity, Stimulant Abuse and Dopamine Receptor Signaling
Edythe D. London
5. Excitotoxicity as a Common Mechanism for Fetal Neuronal Injury with Hypoxia and Intrauterine Inflammation
Irina Burd, Jared Welling, Gokul Kannan, Michael V. Johnston
6. Transcriptional Regulation of Glutamate Transporters: From Extracellular Signals to Transcription Factors
Zila Martinez-Lozada, Alain M. Guillem and Michael B. Robinson
7. The Long and Winding Road: From the High Affinity Choline Uptake Site to Clinical Trials for Malignant Brain Tumors
Pedro R. Lowenstein and Maria G. Castro
8. Choline on the Move: Perspectives on the Molecular Physiology and Pharmacology of the Presynaptic Choline Transporter
Elizabeth A. Ennis and Randy D. Blakely
9. Still NAAG’ing after all these Years: The Continuing Pursuit of GCPII Inhibitors
James J. Vornov, Kristen R. Hollinger, Paul F. Jackson, Krystyna M. Wozniak, Mohamed H. Farah, Pavel Majer, Rana Rais and Barbara S. Slusher
10.  Ultimate Translation; Developing Therapeutics Targeting on N-methyl-D-aspartate Receptor
Guochuan Emil Tsai
11.  The Good and Bad Sides of NAAG
Pamela Khacho, Boyang Wang and Richard Bergeron
12.  The NMDA Receptor and Schizophrenia: From Pathophysiology to Treatment
Darrick T. Balu