A. A. Boulton – författare

In this volume, we hope to cover the malor techniques that are presently being used to analyze the actions of drugs used in psyc- atry. The contributors of the chapters are active researchers who have considerable practical experience with the techniques they are describing, and the emphasis in the chapters is on three types of psychiatric drugs, namely antidepressants, antipsychotics, and anxiolytics. The first chapter, by Curry and Yu, discusses protein binding of psychotropic drugs, with special reference to equilibrium ana- sis as the method of assessment and to lipophilicity correlations. Since many of the drugs used in treating psychiatric disorders are bound extensively to protein, this aspect is of great importance with regard to their therapeutic actions and toxicity, Basic mat- matical models, techniques for the study of protein binding, molecular aspects of protein binding, binding in relation to lipophilicity, indirect approaches to measurement of the fraction of drug bound, the function of protein binding, and tissue binding are among the topics discussed. Chapter 2, by Norman and B- rows, deals with the principles of isotope derivative assays and their applications to antidepressants and antipsychotics; extensive protocols are provided. The third chapter, by Cooper, deals with analysis by gas-liquid chromatography. Sample collection and storage, extraction procedures, column selection, use of internal standards, types of detectors, techniques of application, and - plications to specific drugs are among the topics discussed.

Serendipitous discovery has played an important role m the identification of physiological mechanisms in central and peri- eral neurotransmission. In many cases, the subsequent followup of these discoveries has been substantially aided by previouslyiden- fied natural substances that interfered with these mechanisms. The site of neuromuscular blockade produced by curare extracts, for example, was shown in the 1850s by Claude Bernard, and Sir Henry H. Dale m 1906 discovered the reversal of the pressor effects of adrenal extracts by ergot alkaloids. These findings were the first clues that led eventually to the definition of mcotinic cholinergic receptors and the present classification of adrenergic receptors. In the 1950s many discoveries, including the identification of the catecholamines and 5-hydroxytryptamine in the central n- vous system, followed by the development of specific sensitive biochemical and histochemical methods and the introduction of modern psychotropic drugs led to our increased understanding of chemical transmission and the formulation of theories that attempt to explain the causes of some mental disorders.The finding that hydroxylated derivatives of noradrenaline and- hydroxytryptamine are readily taken up by catecholaminergic or serotonergic neurons, and that this is followed by poisoning and death of the cell, encouraged the use of these compounds for the mapping of central and peripheral catecholamine or- hydroxytryptamine systems, and the mvestigation of the re- vance of these pathways to receptor regulation or behavioral - sponses.

Lipids m the nervous system are major components of the m- branes. The presence of glycolipids in high concentrations is unique for the nervous system. Recent discoverres of the functronal and pathological importance of lipids such as diacylglycerols, polyphosphoinositides, prostaglandins, leukotrienes, docosahexaenoic acid, platelet activating factor, and gangliosides have markedly increased the number of publications on nervous system lipids. Many new methods have been developed. Thus, there IS a need for this volume that is dedicated to that methodo- gy. This volume places all of the methods for lipids into perspective with recommendations concerning the selection of a method for a specific purpose. Lloyd A. Horrocks vii Contents ...Preface to the Series vi Preface...*...xix List of Contributors Lipid Extraction Norman S. Radin 1 1. Introduction ...5 2. Properties of Solvents 2.1. Ethers ...6 8 2.2. Alcohols ...9 2.3. Halocarbons ...9 2.4. Hydrocarbons ...2.5. Miscellaneous Solvents ...10 ...10 3. Storage of Lipid Extracts 14 4. Homogenizers ...15 5. Separating the Extract from the Tissue Residue 15 5.1. Use of Filtration ...16 5.2. Centrifugation ...17 6.Removing Nonlipids from Lipid Extracts 6.1. Removal of Nonlipids by Evaporation and Reextraction ...17 ...17 6.2. Prewashing the Tissue Sample. 6.3. Removal of Nonlipids by Precipitating the Lipids with the Proteins ...18 ...19 6.4. Liquid/Liquid Partitioning ...19 6.5. Removal of Nonlipids by Dialysis 6.6. Separation from Nonlipids by Changing a 21 Partition Constant ...

The two Animal Models in Psychiatry volumes are loosely organized by subject. The first volume contains a number of chapters concerned with schizophrenia, psyc- ses, neuroleptic-induced tardive dyskinesias, and other d- orders that may involve dopamine, such as attention deficit disorder and mania. The second volume deals with affective and anxiety disorders, but also includes chapters on subjects not easily classified as either psychotic, or affective, or an- ety-related, such as aggression, mental retardation, and memory disorders. Four chapters on animal models of schizophrenia or psychoses are included in the present v- ume because of the importance of these disorders in p- chiatry. Likewise, three chapters in the subsequent volume deal with depression. The first of the two volumes begins with an introd- tion by Paul Willner reviewing the criteria for assessing the validity of animal models in psychiatry. He has written - tensively on this subject, and his thorough description of the issues of various forms of validity provides a framework in which to evaluate the subsequent chapters. As will be seen, the remaining chapters in both volumes will refer frequently to these issues. The second chapter, by Melvin Lyon, describes a large number of different procedures that have been p- posed as potential animal models of schizophrenia. This is a departure from the usual format, consisting of detailed - scriptions of specific models.