Central Cholinergic Mechanisms And Adaptive Dysfunctions

Although serious interest in studying the role of central cho linergic processes in psychopathology is just beginning to emerge, experimental literature on the part played by cholinergic mechanisms in brain behavior. reiations is quite extensive. During the past thirty years, cholinergic research has contributed significantly to the characterization and differentiation of adaptive mechanisms in volved in input selection, perception, cortical, autonomic and behav ioral activation, learning, memory, and inhibitory control of behav ioral outputs. To say that dysfunction of one or more of these mech anisms may be at the root of neuropsychiatric illnesses such as schiz ophrenia would be stating the obvious. This book examines the part cholinergic processes might play in dysfunctions of the adaptive processes involved in higher brain func tions and their significance for the pathogenesis, classification, etiology, and treatment of psychopathological conditions. In a series of wide ranging reviews of the available information, the subject is discussed from a variety of perspectives, using data derived from both experimental and clinical research. The purpose is not so much to determine whether cholinergic excess or deficiency is causal in this or that neuropsychiatric syndrome, but rather to try to understand the disease mechanisms in terms of adaptive processes in which cholinergic systems seem to play an important part.

Even if the “weapons of mass destruction” (WMD) and, among them, stocks of organoph- phorus (OP) agents (also referred to as war gases and nerve gases) were not found in Iraq following the US-Iraq war, the relative ease with which these substances can be made from harmless precursors and the low cost of their manufacture will continue to fascinate pow- hungry, ruthless dictators, as well as multinational and international terrorists, particularly as the close relationship between the OP agents and useful insecticides makes it easy to disguise the importation and purchase of small amounts of the precursors. Indeed, the use by Saddam Hussein of a nerve gas against the Kurds and his possible employment of the OP agents during his war with Iran, and the Sarin attack in the Tokyo underground by an extremist religious set magnetized the world with respect to the OP drugs. As these drugs exert their toxicity via their cholinergic action on the nervous, particularly central nervous, system, it is no wonder that the research in the cholinergic ? eld attracts, and merits, our intense attention. These considerations underlie the signi? cance of this book, as Alex Karczmar devotes an entire chapter of Exploring the Vertebrate Central Cholinergic Nervous System to anticholinest- ases (antiChEs), and as he is an acknowledged expert in the ? eld of cholinergic toxicity as well as a consultant to the Surgeon General of the U. S. Army.

In the early 1960s, Dr. Alexander G. Karczmar, Professor of Pharmacology and Experimental Therapeutics at the Stritch School of Medicine of the Medical Center at Loyola University of Chicago, was confronted with a certain technical problem concerning his studies of synaptic transmission by means of microelectrode methods. He thought that the problem might be resolved if he could interest a microelectrode expert such as Dr. Kyozo Koketsu in his studies. Dr. Koketsu was a past member of the Faculty of the Kurume University School of Medicine who as a Research Fellow at the Australian National University had helped Sir John Eccles, subse quently a Nobel Prize winner, in developing microelectrode procedures. After further considering the matter, Dr. Karczmar was pleasantly sur prised to discover that by coincidence Dr. Koketsu was his neighbor, serving at that time as a Research Professor at the Neuropsychiatry Institute of the University of Illinois, College of Medicine of Chicago. This was the beginning of a long relationship, as Dr. Koketsu joined Dr. Karczmar at Loyola as Professor of Pharmacology and Therapeutics and Director of the Neurophysiology Laboratory at the Stritch School of Medicine. It was not long before Dr. Syogoro Nishi-Dr. Koketsu's former colleague on the Faculty of Medicine at Kurume University, and at that time a Research Fellow in Neurophysiology at the Rockefeller Institute in New York joined Drs. Koketsu and Karczmar at Loyola. Although in due time Drs.

There is no area in medicine that has affected biological psychiatry more pro 15 years in en foundly than the developments that have occurred in the last docrinology and more specifically in neuroendocrinology. In the 1960s, the regulation of endocrine function was considered to rest primarily in the feed back system between the pituitary and the secretions of various target organs. In R. H. Williams' Fourth Edition of the Textbook of Endocrinology published in 1968, the chapter on neuroendocrinology did refer to the median eminence gland with a relatively brief mention of various releasing factors that were the subject of ongoing studies. Only six years later, in the Fifth Edition published in 1974, Seymour Reichlin's chapter on neuroendocrinology listed nine specific hypothalamic releasing factors of which three had already been isolated and purified and thus were referred to as hormones. Most recently in the current Sixth Edition, published in 1981, the chapter on neuroendocrinology contains a detailed description of the physiology of the various hypothalamic releasing factors and hormones, but also significant emphasis is given to the various neurotransmitters that have been shown to regulate the synthesis and release of these important hypothalamic hormones. In addition, there appeared for the first time in this classic textbook a chapter on psychoendocrinology. One may wonder why there is so much interest not only in endocrinology but more recently in psychology and psychiatry about psychoneuroendocrine It has been known for some time function. Several reasons may be suggested.

The interaction of neurotransmitters, neuromodulators and neuroactive drugs with receptors localized at the cell surface initiates a chain of molecular events leading to integrated neuronal responses to the triggering stimuli. Major advancements in the characterization and isolation of recep tor molecules have answered many quest ions regarding the nature of the ele ments that determine the specificity in these interactions. At the same time, recent studies have provided evidence that delicate regulation by intracellular enzymatic systems determines the efficiency of the stimulus response coupling process, mediates the interaction between receptors, operates in feedback control mechanisms and transduces signals from the receptors to various effector sites in a highly coordinated fashion. These studies are at the focus of the present volume, which is an outcome of a symposium held at the University of Vermont College of Medicine on March 21-23, 1986, in conjunction with the seventeenth annual meeting of the Amer ican Society for Neurochemistry. The symposium has demonstrated clearly that the concerted efforts of investigators in neurophysiology, biochemis try, pharmacology, cell-biology, molecular genetics, neurology, and psy chiatry are required to achieve better understanding of the processes under lying neuronal responsiveness. This volume includes contributions provided by prominent investigators in all these research areas. We hope that the readers will find here a useful source of information and ideas for stimu lating further studies which may serve to narrow the gap between basic neuroscience research and its clinical implications.

This Festschrift volume in honor of Professor Alexander Karczmar is the outcome of a three-day symposium entitled "Neurobiology of Acetylcholine" held at Loyola University Medical Center from June 3 to 5, 1985. This volume serves two purposes. It expresses the respect and admiration of the contributors to Alex Karczmar, and it provides a forum for detailing recent advances in the cholinergic field which has attracted the undivided and untiring attention of Dr. Karczmar over some 40 years. During this period, the cholinergic system has grown from its infancy to become one of the most studied and understood transmitter systems today. Dr. Karczmar's interest in cholinergic system is appropriately reflected by the range of topics, molecular, cellular, developmental, behavioral and toxicological, that were discussed here. A detailed synopsis of Dr. Karczmar's research and his contributions to the field of cholinergic systems can be found in the following chapter by his close friend and colleague, Dr. George Koelle. We would like to take this opportunity to thank the enthusiastic responses of the participants making this Festschrift a memorable event.