Catecholamines and Behavior · 1

The editor of these volumes has asked me to contribute a brief foreword. When I accepted this honor I suddenly became aware of the enormous progress that has taken place in this field in the 50 years since I began as a medical student, in a humble way, to take interest in the catecholamine system. At about that time some evidence was forthcoming to the effect that catecholamines were an important factor in eliciting emotional reactions, thus secondarily influencing behavior. The great physiologist Walter B. Cannon showed in his classic experiments that when a cat was exposed to a dog it responded not only with overt signs of aversion and dislike, but also with an increased flow of adrenaline from its adrenals. The relationships between catecholamines and behavior have since then become the subject of intense research by physiologists, pharmacologists, and psychologists. Infu­ sion of adrenaline in man was shown to provoke a typical pattern of emo­ tional and behavioral changes. The development of more convenient methods for the measurement of catecholamines in blood and urine led to important new findings. A close association between emotional stress and catecholamine release could be es­ tablished. This was further extended to psychiatric disorders in which characteristic disturbances in catecholamine release patterns were described.

1 Function of the Central Catecholaminergic Neuron: Synthesis, Release, and Inactivation of Transmitter.- 1. Introduction.- 2. Analytical Methods.- 2.1. Biological Methods.- 2.2. Histochemical Methods: Mapping of Catecholaminergic Pathways.- 2.3. Electron Microscopy.- 2.4. Chemical Methods.- 3. The Distribution of the Catecholamines.- 4. Storage.- 5. Biosynthesis of Catecholamines.- 5.1. The Enzymes of Catecholamine Biosynthesis.- 6. Regulation of the Biosynthesis.- 6.1. Tyrosine Hydroxylase.- 6.2. Dopa Decarboxylase.- 6.3. Dopamine-?-Hydroxylase.- 6.4. The Effects of Cyclic AMP on Catecholamine Biosynthesis.- 7. The Metabolic Inactivation of Catecholamines.- 7.1. Catechol-O-Methyltransferase.- 7.2. Monoamine Oxidase.- 7.3. Oxidative-Reductive Pathways for Metabolism of Biogenic Aldehyde.- 7.4. Sulfate Conjugate in the Brain.- 8. Turnover of Catecholamines.- 9. The Release of Noradrenaline.- 9.1. The Uptake of Catecholamines.- 10. Some Aspects of the Pharmacology of Brain Catecholamines.- 10.1. Drugs Acting on Biosynthetic and Inactivating Enzymes.- 10.2. Drugs Acting on the Active Uptake.- 10.3. Drugs Acting on Storage of Catecholamines.- 10.4. Drugs Acting on Monoamine Release and Catabolism.- 10.5. Drugs Acting on Monoamine Receptors.- 11. Conclusions.- 12. References.- 2 Catecholamines in Regulation of Motor Function.- 1. Introduction.- 2. Clinical Evidence for the Involvement of Catecholamines in the Control of Movement.- 2.1. Parkinson’s Syndrome.- 2.2. Huntington’s Disease.- 2.3. Other Dyskinetic Syndromes.- 3. Animal Models for the Study of Catecholamines and Motor Function.- 3.1. Drugs Which Mimic Catecholaminergic Mechanisms.- 3.2. Destruction of Specific Brain Regions and Fiber Tracts.- 4. Conclusion.- 5. References.- 3 Catecholamines in Behavior and Sensorimotor Integration: The Neostriatal System.- 1. Introduction.- 2. Clinical Considerations.- 3. Behavioral Observations.- 4. Anatomical Studies.- 5. Functional Aspects.- 6. Conclusion.- 7. References.- 4 Catecholamines in Activation, Stereotypy, and Level of Mood.- 1. Introduction.- 2. Behavioral Activation and Stereotypy Induced by Amphetamines in Animals.- 3. Possible Role of Noradrenaline in Behavioral Activation and Stereotypy Induced by Morphine.- 4. Effects of Amphetamines and Neuroleptics on Activation, Stereotypy, and Mood in Humans.- 5. References.- 5 Functional Interrelationships of Principal Catecholaminergic Centers in the Brain.- 1. The Role of Biogenic Amines in the Mediation of Certain Central Nervous System Functions.- 2. Results of the Studies.- 2.1. Biochemical Examinations of Healthy Subjects.- 2.2. Examination of Parkinsonian Patients.- 2.3. Examination of Epileptic Patients.- 3. Discussion.- 4. References.- 6 Tremography as a Measure of Extrapyramidal Function in Study of the Dopamine Hypothesis.- 1. Abnormal Movements in Schizophrenia.- 2. Neuroleptic Action of Antischizophrenic Drugs.- 3. Relation Between Neuroleptic and Therapeutic Actions.- 4. Tremography as a Measure of Extrapyramidal Function.- 5. Study of Neuroleptic and Therapeutic Effects.- 6. Evidence from Psychotoxic Effects.- 7. Study of Amphetamine Model Psychosis.- 8. Cardiovascular Effects of Amphetamine Isomers.- 9. The Usefulness of Tremography.- 10. Summary.- 11. References.- 7 Mammalian Biosynthesis of Potential Psychotogens Derived from Dopamine.- 1. Introduction.- 2. Behavioral and Biochemical Effects of 3,4-Dimethoxyphenethylamine.- 3. The Methylation Hypothesis.- 4. Some Aspects of Biological O-Methylation.- 4.1. Catechol-O-methyltransferase.- 4.2. O-Methylating Enzymes Capable of Forming Hallucinogens.- 5. Conclusions.- 6. References.- 8 Regulation of Brain Dopamine Turnover Rate: Pharmacological Implications.- 1. Introduction.- 2. Problems in Interpreting the Compartmentation and the Functional Implications of Turnover Rate Measurement of Neuronal Dopamine.- 2.1. Mathematical Formulation of the Subsystem.- 2.2. Analytical Problems.- 2.3. Compartmentation of Striatal Dopamine.- 2.4. Problems in Measuring Turnover Rate of Striatal DA from the Accumulation of Dopa after Inhibition of Dopa Decarboxylase.- 2.5. The Use of 18O to Measure the Turnover Rate of DA in Terminals and Cell Bodies of Dopaminergic Axons.- 2.6. Interpretation of DA Turnover Rate Measurements in Terms of Dopaminergic Neuronal Function.- 3. Molecular Mechanisms for the Regulation of Dopaminergic Neurons.- 3.1. Regulation of Striatal Tyrosine Hydroxylase.- 3.2. Regulation of Striatal Adenylcyclase.- 3.3. Specificity of Drug Action in Mesolimbic and Nigrostriatal Dopaminergic Systems.- 4. Interaction of the Nigrostriatal Dopaminergic System with Other Neuronal Systems.- 5. Conclusions.- 6. References.