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This book is the proceedings of two symposia, on Proteins of the Nervous System and Myelin Proteins, held as part of the Third Meeting of the International Society of Neurochemistry in Budapest, July 1971. If confirmation of the utility for such a book was needed, it was obtained with the independent publication of a review on Proteins of the Nervous System (1) covering essentially the same ground. This review is an excellent collection of the earlier litera­ ture. The present volume summarizes the more recent advances in this field, and in addition covers those areas, glycoproteins and peptide hydrolases, which were not dealt with by Shooter and Einstein (1). We are most grateful to Miss V. Troeger for typing the man- scripts and to Mr. A. Landmann for assistance with photography. A.N. DAVISON I.G. MORGAN P. MANDEL (1) SHOOTER, E.M. and EINSTEIN, E.R., Ann. Rev. Biochem., 40 (1971) 635.

Proceedings of the 11th European Society for Neurochemistry Meeting held in Groningen, The Netherlandes, June 15-20, 1996

This volume contains the proceedings of the fourth international symposium held in November 1970 at the Texas Research Institute of Mental Sciences in Houston. Leading psychiatrists, biochemists, and pharmacologists from the United States and Great Britain presented new material and reviewed current concepts concerning schizophrenia and the affective disorders, with particular reference to the neurochemical basis of the etiology and chemotherapy of these diseases. Although the multiple mechanisms of mental disease are still not fully understood, substantial progress has definitely been made. The greatest contribution has come through the development of new therapeutic agents that not only provide invaluable help to the mentally ill but serve as chemical tools for studying the biological mechanisms associated with the disease state. Studies concerning the proposed catecholamine and indolealkylamine hypotheses for affective disorders and the possible formation of endogenous. toxins in schizophrenia have stimulated significant new research. This book presents new studies of schizophrenia and the affective disorders in one volume. It is our hope that it represents an effective integration of basic biochemical and pharmacological research with current clinical findings and that it will increase understanding of the etiology of mental disease and provide an impetus for the development of more effective therapeutic agents. We thank Drs. Gordon Farrell, Samuel Gershon, A. Horita, Irwin Kopin, and Joseph Schildkraut for their help with the organization of the meeting and for chairing the corresponding sessions.

This book presents the papers that were delivered at the Satellite Symposium of the International Society for Neurochemistry in Padua, September, 1975. Having such Satellite Symposia was a new experiment for the Society, and all signs, including those from Padua, indicate that it was a very successful experiment, which will be an old tradition for the Society. The large international meeting affords the opportunity for presentations from all areas, for meeting of colleagues from various backgrounds and disciplines. The Satellite Symposia allow people from the same area of interest to discuss their subject in depth, and as such represent meetings of possibly the greatest practical significance for the partici­ pants. The Padua Symposium was no exception: all who particiDated in it could testify to its success in exchanging of information, learning of new approaches, and acqu~r~ng of new ideas, also the strengthening of old friendships, forming of new friendships and new collaborations, and exposing ideas to criticisms, suggestions, discussions. As a sign of the interest and success of the partici­ pants I can mention that all participants have sent in their contributions. Perhaps editors of volumes would anpreciate that the very last came in no later than two months past the deadline.

The first symposium on metabolic compartmentation in brain was held at the Rockefeller Foundation, Bellagio, Italy, July 11-16, 1971; the proceedings CR. Balazs and J. E. Cremer, editors, MacMillan) appeared in 1973. At the conclusion of the first symposium it was decided to assess in 2-3 years the progress in this rapidly developing area. This volume represents the proceedings of an Advanced Study Institute, made possible by a grant from the North Atlantic Treaty Organization, Scientific Affairs Division. Additional generous support by the Wellcome Trust allowed attendance by participants from non-NATO countries. S. Ber! D. D. Clarke D. Schneider xi Introduction The term metabolic compartmentation, as related to the chemistry of the brain, appeared in print for the first time about 15 years ago. The concept was developed in the laboratory of Dr. Heinrich Waelsch as a result of studies related to the metabolism of glutamic acid and glutamine. It was welcomed by a number of neurochemists who felt that the concept had validity and would help explain metabolic phenomena that were otherwise quite puzzling. The concept gradually achieved general acceptance, and by 1971 the amount of information that could profit by being examined from the point of view of metabolic compartmentation had increased sufficiently to warrant a symposium on the subject ('Metabolic Compartmentation in the Brain,'Balazs and Cremer, eds., MacMillan, 1973). Almost all the participants at that initial symposium were present at the second, on which this volume is based.

Neurophysiological recording is the major neuromonitoring technique employed in ICU. In addition, continuous recording of intracranial pressure has proved to provide infomation useful for critical care of the patient with severe brain damage. It is, however, difficult to assess neurochemical and/or metabolic environments of the brain with these conventional neuromoni­ toring techniques. Information regarding these changes, if available on a real-time basis, is undoubtedly useful for patient care. Many important developments in bedside techniques to monitor these changes have been achieved during the last few years. It was the consensus of the editors that a symposium to exchange knowledge concerning recent advances in such techniques would be valuable. With this background, the First International Symposium of Neuro­ chemical Monitoring in ICU held May 20-21, 1994, in Tokyo, Japan. It was not the intention of the organizers that this symposium should survey the whole field of neuromonitoring in ICU. The symposium was thus focused on clinical application of microdialysis, jugular venous oximetry, and near­ infrared spectroscopy, which currently appear to be the most promising techniques for monitoring neurochemical and metabolic changes in the brain in a clinical setting. We termed these techniques collectively as neuro­ chemical monitoring, contrasting them with neurophysiological monitoring in ICU. The concept that has motivated this symposium was to provide an opportunity to exchange up-to-date summaries on issues currently debated for these techniques. This volume is based on the papers presented at the symposium.

ment of mental retardation as in the young human. These two facts together suggest that the disrup­ tion of brain protein synthesis by high phenylala­ mine levels in infants may account for the mental retardation observed later in these children. Much work remains to be done to confi~m this possibility. However, it is clear from the review and research described by Waisman that neurochemis­ try has the tools that will lead to an understand­ ing of - and therefore perhaps control of - these inborn errors of metabolism which otherwise can lead to lifetimes of personal tragedy for the af­ fected persons and their families. The final section of these Proceedings deals with neurochemical processes which occur during brief behavioral experiences, particularly learn­ ing. The reported research has been motivated by the search for processes which underlie the encoding of memory, although the identification of these processes is not yet certain in the various studies. Geller and Jarvik begin with a discussion of short term and long term memory storage processes, and describe the induction of retrograde amnesia by various agents as evidence for these processes.

It is increasingly evident that polyunsaturated fatty acids (PUFA), which in the past were often believed to be mere components of cellular membranes of neural tissue, are actually major determinants of the functional properties of neural cells and are intimately involved in brain disease processes. The two families of PUF A, which are derived from the essential polyenes, linoleic (18:26) and a-linolenic (18:33) acids, constitute a major proportion (-30%) of the total fatty acids esterified to brain phospholipids. Each family is distributed in membranes in a highly specific manner with respect to brain region, cell type, and position within each of the phosphoglycerides. Unlike their behavior in other organs, the PUF A components of brain turn over slowly and are relatively resistant to dietary modification. Their unique distribution and stability suggest that they play an important role in determining the functional properties of neural cells. However, until recently very little was known regarding the precise nature of their involvement.

The contents of this book are the presentations of a Symposium on'Memory and Transfer of Information', held at Gottingen, May 24-26, 1972. One of the main reasons for organizing this Symposium was to stimulate interdisciplinary discussion between sci­ entists working in the field as a whole. Most of the pre­ vious meetings dealing with memory and transfer of infor­ mation have tended to be rather limited in scope. The pres­ ent Symposium covered a wide range of topics, including neurophysiological, neuropharmacological, neurochemical, behavioral and clinical aspects of learning and chemical transfer of information, presented by specialists in these areas. The Proceedings of the meeting present a large number of previously unpublished results, e.g., recent experiments in neurophysiology and neurochemistry, new approaches to chemical transfer of learned information, experiments using synthetic scotophobin and drugs influencing learning and behavior. The importance of interdisciplinary discussion is perhaps most clearly emphasized by the advances in neuro­ chemical micromethods which are of particular interest to scientists working on the chemical transfer of information. Only such interdisciplinary collaboration between highly specialized scientists guarantees further progress and deeper insight into the complex, and until now little under­ stood, mechanisms of that most intricate of organs, the brain. Hans Peter ZIPPEL vii CONTRIBUTORS BRADLEY, P.B. Department of Pharmacology, Medical School, Birmingham B1S 2TJ, England BYRNE, W. L. ~'; Department of Biochemistry. University of Tennessee. College of Basic Medical Sciences. Memphis. Tennessee 38103. U.S.A. CREUTZFELDT, O.D.

Few can deny the paramount importance of the neurosciences, undoubtedly one of the most challenging fields in contemporary science. Recent years have witnessed the awakening of interest in brain research by many dis­ tinguished investigators from other branches of science, which has made possible the multidisciplinary approach needed for the complex problems of this field. The present book, which deals with one aspect of this research, is the result of the symposium held under the auspices of the New York State Research Institute for Neurochemistry and Drug Addiction in April 1968. It has become clear that brain proteins are involved in all aspects of mental function and dysfunction, and the present volume documents the latest advances in our knowledge (advances made to a large extent by con­ tributors to this volume). The chapters not only convey some of the enthu­ siasm and wonderful, cooperative spirit of the many excellent scientists ex­ ploring the brain, and their wealth of ideas; they also illustrate the many approaches from which cerebral proteins can be studied in a meaningful manner. In some areas even preliminary evidence is worth discussing: e.g., it is an exciting achievement that we can begin to apply the disciplines of bio­ chemistry to phenomena of learned behavior and information handling.

Neurological disorders cause untold suffering and financial burden to hundreds of thousands of people, not only to the patients, but also the relatives and society. As of today, though numerous scientists and clinicians have devoted their efforts to understand and combat these diseases, there is still no cure or satisfactory solution to the problems. Furthermore, the brain is the most essential organ of a human being. Realizing the importance of the brain, the president of the United States, George Bush, declared the 90s as the Decade of the Brain in January, 1992. Being in neuroscience research for almost three decades, I initiated, planned and organized the first international neuropharmacology symposium. After long negotiation and fund raising, with the assistance and moral support of Dr. Abel Lajtha, director ofthe Center ofNeurochem­ istry in New York, USA, we finally successfully put the program together. The Sun Yat-sen Foundation in China supported all the local expenses of the symposium and Sun Yat-sen University of Medicine in Guangzhou, China served as host organization. The symposium was held in Guangzhou, China, November 9-11,1992, the eve of Dr. Sun Yat-sen's birthday. Dr. Sun Yat-sen was born in Cui Heng Cun, on the outskirts of Guangzhou, China on November 12, 1866. He finished his high school education in the British and American Christian school in Honolulu, where he was exposed to Western influence. He had been long frustrated and discontented with the backwardness and corruption of the Ching Dynasty.

The nature and diversity of presentations at the second International Conference on Insect Neurochemistry and Neurophysiology (ICINN--86) held at the University of Maryland on August 4-6. 1986, attest to the vital­ ity and broad scope of research in insect neuroscience. The present vol­ ume is a written account of the invited lectures, contributed papers, and posters presented at the conference, and as such, serves as a fair indica­ tor of the trends in current research in this field here and abroad. The principal portion of this book consists of seven review papers that were presented by invited speakers. Although the topics vary wide­ ly, they reflect on and emphasize the main theme of the conference, i. e., the nature and function of molecular messengers that communicate be­ meen the central nervous system and organs or tissues involved in the growth, development, reproduction, and behavior of insects. This empha­ sis is continued in the following three sections on neurochemistry, neuro­ physiology, and neuroanatomy, although no conscious effort was made by the organizers to highlight these particular fields of neuroscience. It is evident that the recent advances in both physical and chemical analyti­ cal techniques have made possible the acquisition of structurally defined probes, the long sought-after tools for unraveling the secrets of endogen­ ous communication. Each section of short papers derived from the oral and poster presentations at the conference is prefaced by an overview that highlights and summarizes the section's content.

In March, 1974, an International Symposium was held at the Harmonie Club in New York to discuss a highly pertinent problem in today's research: the'Rele­ vance of the Animal Psychopathological Model to the Human.'This meeting was sponsored by the Kittay Foundation, which brought together an outstanding group of scientists involved in widely different fields of research. This volume, it is hoped, will convey the tone of lively and cordial exchange between inter­ nationally renowned investigators, including Dr. I. Eibl-Eibesfeldt from Germany, Dr. Robert A. Hinde from England, Dr. Edward F. Domino from Michigan, and Dr. Pierre Pichot from France, Chairman of the Steering Committee. In his welcoming address, Mr. Sol Kittay reminded us that man has achieved remarkable control over his environment but not over himself, and he suggested that we should reexamine our ancestral origins, and search in animal behavior for clues to the understanding of normal and abnormal behavior in man.

Alcohol abuse and alcoholism are international problems whose costs economical­ ly, psychologically and medically have been well documented. Alcohol is a unique drug in that the effects of excessive use can have a deleterious effect on most if not all organs of the body. The brain is one of the organs most affected by excessive alcohol consumption. Effects on the brain can be seen in cognitive function, brain structure and neurochemistry. Over the past few years, there have been significant advances made in understanding how alcohol affects brain neurochemistry. This book examines four major areas, i. e., membrane lipids, receptors and ion channels, second messengers, and gene expression, where significant advancements have been made. The book is divided into four sections based on the four major areas. In each section, data are examined that cover a range of approaches from in vitro to in vivo studies. The section on membrane lipids includes recent developments in how ethanol affects membrane cholesterol domains, polyunsaturated fatty acids, the cause and consequences of phosphatidylethanol formation, and the modulation of membrane protein function by lipid-protein interaction. The second section comprises chapters on NMDA and 5-HT3 receptors, including new aspects on alcohol neurotoxicity and the molecular heterogeneity that may underlie differences in alcohol sensitivity as well as chapters on GABA-gated chloride flux, and calcium channels.

In 1970 I gave up the chairmanship of the Department of Pharmacology at Stanford University Schoel of Medicine to devote full time to basic and clinical research on problems of drug addiction. In 1971 I developed the method of radioligand binding that led to the important characterization of opioid receptors in several laboratories. The extraordinary specificity of these receptors for morphine and related opiates suggested the likelihood that there were naturally occurring morphine-like molecules in the brain and other tissues. The systematic search for these molecules culminated in 1979 in the discovery, by my group, ofthe dynorphin peptides-one of the three families of opioid peptides, the first of which (the enkephalin family) had been discovered in Aberdeen, Scotland, in 1975. I also became involved in clinical research on the pharmacologic treatment of heroin addicts, for which I established the first large methadone mainte­ nance treatment program in California. My basic and clinical research experience convinced me that an institution encompassing laboratory research, studies on normal human volunteers, and treatment research, under a single roof, could expedite progress in understanding the drug addictions. That concept was transformed into reality by the founding, in 1974, of the Addiction Research Foundation of Palo Alto, California. The funds for construction of a laboratory were provided by a generous grant from the Drug Abuse Council (a consortium of several foundations), the president of which was Thomas L. Bryant.

The vast growth of knowledge in recent years concerning the functional role of serotonergic systems in central nervous system function prompted the organization of the symposium. The organiz­ ing committees felt at the onset that the field of serotonin research had grown so rapidly that it would be impossible to cover every aspect of it in individual symposia. Thus it was felt that certain areas of research had to be omitted due to time constraints, and we extend an apology to the researchers in areas not included in these proceedings. Rather it was hoped to provide a balance overview of the field, starting with the anatomy of serotonergic systems and proceeding to the level of the serotonergic receptors at the cell membrane, and then inside the neuron to discuss the regulation of serotonin bisynthesis and integration within indole­ mine systems. The functional aspects of serotonergic transmission focused on the emerging role of this amine in the processing of nociceptive information, singly or in tandem with other neurotran­ smitters or neuromodulators. A separate symposium dealt with a variety of animal models suitable for the analysis of the role of serotonin in behavior, and finally led to the evaluation of serotonin metabolism in the study of abnormal human behavior. The editors would like to dedicate these proceedings on /Serotonin - Current Aspects of Neurochemistry and Function/ to two pioneers in this field, Dr. Irving Page and Dr. Maurice Rapport.

This volume summarizes the evolution and physiology of GnRH molecules and receptors, and provides insight as to how social behavior influences cellular and molecular events in the brain from a comparative perspective.The chapters in this volume are divided into three major sections: Development and Cell Migration, GnRH Receptors, Physiology and Regulation. The review papers arose primarily from presentations made at the Second International Symposium on the Comparative Biology of GnRH, held in Penang, Malaysia, June 2-4, 2001; a satellite symposium in conjunction with the XIV International Congress of Comparative Endocrinology, Sorrento, Italy. In addition, leading neuroscientists doing cutting-edge research in the field of GnRH were invited as authors to make this volume a valuable reference.

The study of purinergic mechanisms has for long been focused on the actions of the nucleoside adenosine, whereby the contribution of nucleotides to the signaling systems has been underestimated.Based on the proceedings of a IUPHAR Satellite Conference held in Leipzig, Germany, this book offers a comprehensive update and overview of nucleotide release, the structure and function of nucleotide receptors, nucleotide-metabolizing ecto-enzymes as well as the physiological functions of nucleotides in the nervous system. The physiology and molecular biology of receptors for ATP and other nucleotides are examined, as are the physiology and molecular biology of enzymes that hydrolyze extracellular nucleotides.At present, a pharmacology of the nucleotide signaling system is being developed. Of particular interest is the production of receptor subtype-specific antagonists and of drugs that selectively affect the extracellular lifetime of the nucleotide.An excellent source of reference for institutes of pharmacology, biochemistry, neurology, zoology, and physiology, and for the pharmaceutical industry.

Alcohol and Opiates: Neurochemical and Behavioral Mechanisms contains the proceedings of the 1976 conference,''The Neurochemical and Behavioral Mechanisms of Alcohol and Opiate Dependence'', held in New York. The papers focus on the commonalities and distinctions of alcohol and opiates in terms of neurochemical and behavioral mechanisms. It also highlights key research findings on alcohol and drug dependence as well as advances in the understanding of opiate neurochemistry and the nature of alcoholism. Organized into two sections comprised of 22 chapters, this compilation begins with an overview of the various techniques used to produce and to measure alcohol dependence using animal models. It then discusses the neurochemical components of ethanol dependence, the pharmacogenetics of alcoholism, and the effects of alcohol on behavioral performance. The remaining chapters examine the pharmacology of isoquinoline alkaloids and ethanol interactions, the neurochemical aspects of opiate dependence, the pharmocological heterogeneity of narcotic receptors, and the pharmacology of endogenous opiate-like peptides. The book also introduces the reinforcement of behavior by morphine injections and the metabolic stereospecificity of opiate agonist and antagonist drugs. It concludes with an assessment of future research directions concerning opioid peptides (endorphins). This book is a valuable source of information for those seeking to build clinical programs designed to alleviate the sociological and medical ills associated with alcohol and opiate abuse and drug dependency.

Wenner-Gren Center International Symposium Series, Volume 5: Mechanisms of Release of Biogenic Amines provides information pertinent to the fundamental aspects of the release of biogenic amines. This book discusses the physiology, biochemistry, and pharmacology of the biogenic amines. Organized into 39 chapters, this volume begins with an overview of the release of amines, which is implicated in functional disturbances characteristic of different diseases. This text then examines the concepts of cell structure that are significant to the release of neurohumoral agents. Other chapters consider the fluorescence reaction, which made it possible to work out a practical histochemical procedure. This book describes as well a few examples in which the monoaminergic transmitter is not revealed as a diffuse cytoplasmic fluorescence. The final chapter deals with acetylcholine as the only brain amine investigated, which could be influenced by the tremorgenic agents during the period of tremor. This book is a valuable resource for biochemists, morphologists, pharmacologists, and physiologists.

Biochemical Factors Concerned in the Functional Activity of the Nervous System presents the biological aspects concerned in the functional activity of the nervous system. This book covers several interesting topics concerning the central nervous system, including phospholipids, RNA synthesis, nerve impulse flow, and nerve growth factor. Comprised of 213 chapters, this book begins with an overview of the electron micrographs of calcium–ATP–phospholipid complexes. This text then examines the biochemical and histochemical studies on sectioned rat spinal cords, which demonstrated two types of monoamine-reducing drugs. Other chapters consider the diversity of antagonistic relations between the thiamine derivatives and vitamin B6, which is manifested by changes in the glutamate–GABA, histidine–histamine, tryptophan–serotonin, and tyrosine–noradrenaline systems. This book discusses as well the influence of a conditioned avoidance training experience on the incorporation of radioactive uridine into the RNA of mouse brain. The final chapter deals with the amino acid-incorporating activity of cerebral polyribosomes. This book is a valuable resource for biochemists, neurologists, pharmacologists, and biophysicists.

Opiate Receptors and the Neurochemical Correlates of Pain, Volume V, documents the proceedings of the 3rd Congress of the Hungarian Pharmacological Society held in Budapest, 1979. The congress offered a good opportunity to stimulate discussions and exchange of ideas between scientists from various countries who approach the problem of narcotics and pain mechanisms in different ways. The 27 contributions in this volume have enriched knowledge in this rapidly expanding field of pharmacology. This volume begins with a discussion of opiate receptors. The results suggest the interaction of various morphine-like drugs with different opiate receptor populations. The existence in nerve tissue of specific opiate receptors binding morphine and other opioids has led to the assumption of endogenous ligand for opiate receptors. One section of the present volume is devoted to enkephalins and endorphins, their structure-activity relationships, interactions with transmitter and other systems, their behavioral effects, and to factors controlling their release. Some other aspects of nociception; the pathways involved in the mode of action of different types of analgesics, e.g. narcotics and non-narcotics; and their relations to inflammation and active substances, such as prostaglandins and substance P, are discussed from various aspects.

Neurochemistry of the Retina covers the proceedings of the International Symposium on the Neurochemistry of the Retina held in Athens, Greece, on August 28 – September 1, 1979. This book mainly focuses on the retina and its neurochemistry. This text is divided into eight major parts. The first part discusses the composition, metabolism, and biogenesis of membrane components. This book then explains the biochemical approaches to the study of visual cells and their relationship with the pigment epithelium, photorector shedding, and circadian rhythm. Chemical transmission of nerve signals is also tackled. This text also looks into the biochemical aspects of photoreceptor structure and function; cyclic nucleotides; and biochemical and pharmacological approaches to study the entire retina. This book concludes by explaining the neurochemical studies in retinal diseases and future research and prospective of the subject. This publication will be invaluable to ophthalmologists and students of ophthalmology.

This volume looks at the associative mechanisms of the brain, particularly of the cortico-limbic and diencephalic systems, and also at the macromolecular effects on them, by integrating the contributions of various disciplines converging on one subject and from different points of view. It addresses the question of how so many different activity levels — the biochemical, physiological, and psychological ones — interact in integrative processes. The topics treated include brain reverberating systems and associative phenomena; long-term potentiation, learning, and memory; gene activity and brain activity; and gene expression and information processing during sleep.

Biogenic Amines

Neurochemical Aspects of Hypothalamic Function covers the proceedings of the Second International Meeting of the International Society for Neurochemistry, held in Milan, Italy, on September 1969. The one-day symposium focuses on the neurochemical aspects of hypothalamic function and their relation to secretion of anterior pituitary hormones. This book contains seven chapters that emphasize the relationships among the effects of environmental stimuli and observable changes in catecholamines in the hypothalamus, indoleamines in the pineal, the hypophysiotropic hormones of the hypothalamus, and secretion of anterior pituitary hormones. This text further explores some important interactions between the external environment, brain, and anterior pituitary, as well as feedback on the brain and anterior pituitary by body target organs, with a particular emphasis on their function as a unit. This book is an ideal source for neucochemists, neurologists, and researchers who are interested in the hypothalamic function.

Metabolism of the Nervous System contains the proceedings of the 2nd International Neurochemical Symposium, held at Aarhus, Denmark, in July 1956. The book discusses the molecular structure and morphology of the adult nervous tissue; the chemical composition and cytochemical localization of adult nervous tissue; and the permeability and blood-brain barrier. The text also describes topics on electrolytes and nervous conduction; the metabolism of isolated nerve and ganglion; and the metabolism of the brain in vivo. The metabolism of brain tissue preparations in vitro; energy metabolism and coenzymes in relation to the nervous system; and lipid and fatty acid metabolism are also considered. The book further tackles nucleic acid metabolism; protein and amino acid metabolism; and cholinergic and non-cholinergic transmission. The text also discusses other pharmacologically active compounds related to the adult nervous tissue.