The noted French physiologist Claude Bernard was fond of noting that "experimental ideas are often born by chance, with the help of some casual observation. " If history teaches us, we realize that this statement is as true today as it was 100 years ago. Today, however, we are luckier. We have, generally, some basis from previous work so that we can follow a line of research and thus provide even our most fundamental studies with an air of scientific respectability. Present-day research is rather like the working of a giant crossword puzzle where some of the letters or even words have been com- pleted and the approach toward a relatively confident solution is a matter of juggling a series of permutations. I often wonder, though, how it was for the early brain researchers, who had very few letters, and, even less, no words, completed in their research puzzles to augment intelligent casual observation. By "early," I refer to nineteenth or early twentieth century investigators-men like Cajal, Sherrington, Pavlov, and Sechenov, whose investigations did more to advance their field in a span of 50 years than all of the cumulative previous work done on the brain and nervous system since the ancient Greeks.

Table of Contents:
1. Metabolism of Monoamines.- 1.1. Biochemistry of Catecholamines in Brain.- 1.1.1. Conversion of Phenylalanine to Tyrosine.- 1.1.2. Conversion of Tyrosine to L-Dopa.- 1.1.3. Conversion of L-Dopa to Dopamine.- 1.1.4. Conversion of Dopamine to Noradrenaline.- 1.1.5. Conversion of Noradrenaline to Adrenaline.- 1.1.6. Biosynthesis of Catecholamines in the Brain.- 1.2. Biochemistry of 5-Hydroxytryptamine (Serotonin).- 1.2.1. Conversion of Tryptophan to 5-Hydroxytryptophan.- 1.2.2. Conversion of 5-HTP to 5-HT.- 1.3. Inactivation of Monoamines.- 1.3.1. Catechol-O-Methyltransferase.- 1.3.2. Monoamine Oxidase.- 2. Methods of Studying Cerebral Monoamines and Their Enzymes.- 2.1. Evaluation of Metabolites Excreted in Urine.- 2.2. Labeling and Autoradiographic Study of Monoamines.- 2.3. Ultrastructures: Electron Microscope Studies.- 2.4. Histochemical Fluorescence Method.- 2.4.1. Procedure for the Histochemical Fluorescence Reaction.- 2.4.2. Catecholamines in the Human Hypothalamus.- 3. Normal and Abnormal Physiology of Monoamines in the Central Nervous System.- 3.1. Monoamine Uptake and Distribution in Brain.- 3.2. Localization of Intraneuronal and Diffuse Monoamines.- 3.3. Localization of Brain Monoamine Nerve Terminals.- 3.4. Monoamines as Transmitters in the Central Nervous System.- 3.4.1. Monoaminergic Pathways.- 3.4.2. Monoamines in Brain Embryonic Development.- 3.4.3. Vascular Mechanisms and Catecholamines.- 3.5. Neuropharmacology and Behavior.- 3.6. Inhibition and Release of Monoamines by Drugs.- 3.7. Sleep Mechanisms.- 3.7.1. Slow Sleep and Serotonin.- 3.7.2. Paradoxical Sleep and Noradrenaline.- 3.8. Blood-Brain Barrier.- 4. Neuropsychopathology.- 4.1. Genetic Factors.- 4.1.1. Phenylketonuria (Phenylpyruvic Oligophrenia).- 4.1.2. Hepatolenticular Degeneration (Wilson's Disease).- 4.1.3. Hartnup Disease.- 4.1.4. Mongolism (Down's Syndrome).- 4.1.5. Familial Dysautonomia (Riley-Day Syndrome).- 4.2. Metabolism in Psychoses.- 4.2.1. DIMPEA Theory.- 4.2.2. Serotonin Hypothesis.- 4.2.3. Catecholamine Hypothesis.- 4.2.4. Various Affective States and Stress.- 4.2.5. Psychotomimetic Model Psychoses: LSD-25.- 4.3. Neuropathological States.- 4.3.1. Neuroendocrine States.- 4.3.2. Experimental Seizures.- 4.3.3. Brain Trauma.- 4.3.4. Parkinson's Disease.- Appendix: Abbreviations Used in Text.- References.