Solomon Snyder has been instrumental in the establishment of modern psychopharmacology—as a pioneer in the identification of receptors for neurotransmitters and drugs and in the explanation of the actions of psychotropic agents. Science and Psychiatry is a collection of some of his best scientific papers, publications ranging over forty years that represent important advances in psychopharmacology and molecular biology. Audacious and unanticipated when they first appeared, these papers opened up new areas of understanding and revolutionized the modern study of the brain. Republished here, they show why fundamental research into the “messengers of the mind” is as essential for clinicians as for researchers.
Many of these papers have clear clinical relevance, offering insight into modern neuroscience to help make sense of the bewildering array of available psychotropic medications and point the way toward more effective and safer agents. Others describe the underpinnings of psychopharmacology that practitioners need to know, especially regarding the role of receptors in drug action. Each of the nine groups of research articles is accompanied by a commentary by a well-known authority, putting the discoveries in perspective and providing a broad overview of subjects ranging from characterization of the enkephalins to serotonin receptor subtypes. The final set of papers focuses on apoptosis, the general process of cell suicide, where Snyder’s work with bilirubin holds promise for treating neurodegenerative disorders. And in a closing piece, “The Audacity Principle in Science,” Snyder speculates about factors conducive to creativity and efficacy in scientific discovery.
The articles particularly describe four groups of extraordinary discoveries for which Snyder is widely recognized:
- Identification of opiate receptors, providing keys to understanding pain perception
- Characterization of the IP3 receptor, exploring its role as a target for lithium treatment in manic-depressive disorders
- Establishment of nitric oxide as a transmitter in the brain, radically transforming conceptualizations of neurotransmission
- Discovery that D-serine is the normal stimulus for the glycine site of the NMDA receptor, providing new insight into the regulation of the receptor important for learning and memory
Hailed as one of the preeminent scientists of the past twenty years, Snyder is a consummate researcher who confesses to remaining obsessed with the need to “think thoughts no one else has thought before.” Science and Psychiatry
clearly shows how that urge accounts for the diversity of challenges he has taken on as it conveys the origins of modern psychopharmacologic practice.
Foreword. Introduction. Part I: Discovery and Characterization of the Opiate Receptor. Commentary: radioligand binding methodologies: new inventions, new directions. Opiate receptor: demonstration in nervous tissue. Opiate agonists and antagonists discriminated by receptor binding in brain. Historical review: opioid receptors. Part II: Characterization of the Enkephalins. Commentary: the discovery of endogenous opiates and their receptors: a Snyderian saga of skill and judgment. Opiate receptor in normal and drug-altered brain function. Morphine-like peptides in mammalian brain: isolation, structure elucidation, and interactions with the opiate receptor. Opioid peptide enkephalin: immunohistochemical mapping in rat central nervous system. Part III: Dopamine Receptors and Influences of Neuroleptics. Commentary: dopamine receptor binding and its therapeutics. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain. Dopamine receptors, neuroleptics, and schizophrenia. Part IV: Drug Effects Explained as Actions on Neurotransmitter Receptors. Commentary: perspectives on simplicity and discovery. Antischizophrenic drugs and brain cholinergic receptors: affinity for muscarinic sites predicts extrapyramidal effects. Tricyclic antidepressants: therapeutic properties and affinity for alpha-noradrenergic receptor binding sites in the brain. Part V: Drug Actions and Serotonin Receptor Subtypes. Commentary: clinical data stimulation of basic research: the far-reaching clinical significance of serotonin receptor subtype identification. Long-term antidepressant treatment decreases spiroperidol-labeled serotonin receptor binding. Two distinct central serotonin receptors with different physiological functions. Part VI: Inositol Phosphates and Actions of Lithium. Commentary: lithium, second messengers, and downstream effects. Lithium blocks a phosphoinositide-mediated cholinergic response in hippocampal slices. Solubilization, purification, and characterization of an inositol trisphosphate receptor. Second messenger systems and psychoactive drug action: focus on the phosphoinositide system and lithium. Purified inositol 1,4,5-trisphosphate receptor mediates calcium flux in reconstituted lipid vesicles. Part VII: Nitric Oxide as a Neurotransmitter. Commentary: just say "yes": Snyder's approach to the difficult problem of NO. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Cloned and expressed nitric oxide synthase structurally resembles cytochrome p450 reductase. Behavioral abnormalities in male mice lacking neuronal nitric oxide synthase. Part VIII: Amino Acids as Neurotransmitters. Commentary: disruptive science: incongruent findings lead to novel insights into how the brain works. d-Aspartate localizations imply neuronal and neuroendocrine roles. Serine racemase: a glial enzyme synthesizing d-serine to regulate glutamate-N-methyl-d-aspartate neurotransmission. Serine racemase: activation by glutamate neurotransmission via glutamate receptor interacting protein and mediation of neuronal migration. Part IX: Neural Messengers of Cell Life and Death. Commentary: beyond neurotransmitters. Cytochrome c binds to inositol 1,4,5-trisphosphate receptors, amplifying calcium-dependent apoptosis. Bilirubin benefits: cellular protection by a biliverdin reductase antioxidant cycle. S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Part X: What Makes for Creative Discovery in Science? Commentary: what creates creative science and scientists? The audacity principle in science. Index.
"An important aspect of the education and training of each generation of new scientists is understanding the history of a field. The book of Science and Psychiatry: Ground-Breaking Discoveries in Molecular Neuroscience by Dr. Solomon Snyder is a wonderful work from which to gain such insights. The personal history of Dr. Snyder’s many discoveries will provide many generations of scientists insights they could never otherwise achieve."—Edward Scolnick, M.D., Director, the Psychiatry Initiative Director, the Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
"This volume summarizes and highlights the professional career of Solomon Synder, an extraordinarily creative neurobiologist and biological psychiatrist and one of the preeminent leaders in the field of neuroscience for over three decades. The volume includes a collection of some of Synder's most seminal contributions in nine different subject areas in the field of biological psychiatry. A particularly charming aspect of the book is the glowing testimonials to Snyder's great contributions by almost a dozen of the most distinguished leaders in this field."—Paul Greengard, Ph.D., Vincent Astor Professor, Director, Fisher Center for Alzheimer's Research, The Rockefeller University
"Solomon Snyder is one of the greatest neuroscientists of our generation or, for that matter, any generation. This wonderful book, by anthologizing his sentinel papers, presents the brilliant insights of his career, insights that have shaped the way we understand the brain. This volume should take its place on the shelves of every scientist engaged in biological research who seeks inspiration through a glimpse into the mind of a true genius."—Kenneth L. Davis, M.D., President & CEO, The Mount Sinai Medical Center, Professor of Psychiatry, Mount Sinai School of Medicine
Solomon H. Snyder, M.D., is Distinguished Service Professor of Neuroscience, Pharmacology, and Psychiatry at Johns Hopkins University.