The studies discussed here have shown a fairly consistent relationship between the effects of drugs on biogenic amines, particularly norepinephrine, and affective or behavioral states. Those drugs which cause depletion and inactivation of norepinephrine centrally produce sedation or depression, while drugs which increase or potentiate brain norepinephrine are associated with behavioral stimulation or excitement and generally have an antidepressant effect in man (Table 1). From these findings, a number of investigators have formulated the concept, designated the catecholamine hypothesis of affective disorders (6), that some, if not all, depressions may be associated with a relative deficiency of norepinephrine at functionally important adrenergic receptor sites in the brain, whereas elations may be associated with an excess of such amines. It is not possible either to confirm or to reject this hypothesis on the basis of currently available clinical data. Although there does appear to be a fairly consistent relationship between the effects of pharmacological agents on norepinephrine metabolism and on affective state, a rigorous extrapolation from pharmacological studies to pathophysiology cannot be made. Confirmation of this hypothesis must ultimately depend upon direct demonstration of the biochemical abnormality in the naturally occurring illness. It should be emphasized, however, that the demonstration of such a biochemical abnormality would not necessarily imply a genetic or constitutional, rather than an environmental or psychological, etiology of depression. Whereas specific genetic factors may be of importance in the etiology of some, and possibly all, depressions, it is equally conceivable that early experiences of the infant or child may cause enduring biochemical changes and that these may predispose some individuals to depressions in adulthood. It is not likely that changes in the metabolism of the biogenic amines alone will account for the complex phenomena of normal or pathological affect. Whereas the effects of these amines at particular sites in the brain may be of crucial importance in the regulation of affect, any comprehensive formulation of the physiology of affective state will have to include many other concomitant biochemical, physiological, and psychological factors. Although in this review of the relationship of biogenic amines to affective state relatively little has been said concerning the intricate set of environmental and psychological determinants of emotion, the importance of these factors must be stressed. The normally occurring alterations in affective state induced by environmental events is well known to all, from personal experience. The interactions between such environmental determinants of affect, various physiological factors, and the complexity of psychological determinants, including cognitive factors derived from the individual's remote and immediate past experiences, have received only limited study under adequately controlled conditions. It may be anticipated, however, that this will prove to be a particularly fruitful area for future research, for only within such a multifactorial framework may one expect to understand fully the relationship of the biogenic amines to emotional state.

https://science.sciencemag.org/content/sci/156/3771/21.full.pdf

Biogenic Amines and Emotion

Physical exercise influences the central dopaminergic, noradrenergic and serotonergic systems. A number of studies have examined brain noradrenaline (norepinephrine), serotonin (5-hydroxytryptamine; 5-HT) and dopamine with exercise. Although there are great discrepancies in experimental protocols, the results indicate that there is evidence in favour of changes in synthesis and metabolism of monoamines during exercise. There is a possibility that the interactions between brain neurotransmitters and their specific receptors could play a role in the onset of fatigue during prolonged exercise. The data on the effects of branched chain amino acid (BCAA) supplementation and 'central fatigue' seem to be conflicting, although recent studies suggest that BCAA supplementation has no influence on endurance performance. There are numerous levels at which central neurotransmitters can affect motor behaviour; from sensory perception, and sensory-motor integration, to motor effector mechanisms. However, the crucial point is whether or not the changes in neurotransmitter levels trigger or reflect changes in monoamine release. Until recently most studies were done on homogenised tissue, which gives no indication of the dynamic release of neurotransmitters in the extracellular space of living organisms. Recently, new techniques such as microdialysis are voltammetry were introduced to measure in vivo release of neurotransmitters. Microdialysis can collect virtually any substance from the brain of a freely moving animal with a limited amount of tissue trauma. This method allows measurement of local neurotransmitter release during on-going behavioural changes such as exercise. The results of the first studies using these methods indicate that the release of most neurotransmitters is influenced by exercise. Although the few studies that have been published to date show some discrepancies, we feel that these recently developed and more sophisticated in vivo methods will improve our insight into the relationship between the monoamine and other transmitters during exercise. Continued quantitative and qualitative research needs to be conducted so that a further understanding of the effects of exercise on brain neurotransmission can be gained.

Exercise and Brain Neurotransmission

Increased turnover of norepinephrine in the rat cerebral cortex during stress: role of the locus coeruleus.

Stress and Catecholamines

The behavioral effects of early malnutrition and early environmental isolation were observed in male rats. Dietary and environmental manipulations occurred during the first 7 weeks of life, after which followed a 10-week recovery period. On the basis of several different responses, it was found that the behavioral effects of early malnutrition were exaggerated by the environmental isolation. In most cases, the behavioral effects of early malnutrition were completely eliminated by supplying "additional stimulation" early in life. Two theoretical mechanisms are proposed to explain these findings.

http://science.sciencemag.org/content/sci/176/4030/68.full.pdf

Eugene W. Lariviere

Papers

Effects of stress and d-amphetamine on rat brain catecholamines.