The Effect of Gonadal Steroids and Altered Tryptophan Metabolism on behaviour

Abstract

Gonedal steroids have been shown to affect tryptophan metabolism in both brain and body, end are thus thought capable of altering the rate of 5-hydroxyptamine synthesis, end consequently, serotoninergic neuronal activity. Subsequent behavioural changes should result, and a primary aim of the research was to elucidate such changes within specific behavioural parameters. In order to discern more exactly the effect of gonadal steroids on behaviour, other, more specific, alterations in tryptophan metabolism were undertaken using various pharmacological manipulations. Alterations in behaviour after such manipulations were then observed, within the previous behavioural paremeters. A clinical study was carried out in order to ascertain the effect of gonadel steroids, in the form of the oral contraceptive, on plasma tryptophan, mood and behaviour in the human female. The results suggest that gonadal steroids influence behaviour by increasing 5-hydroxytryptamine synthesis. In general, such an effect led to an exhibition of behaviourel depression, manifested as reduced locomotor activity and startle response magnitude. A paradoxical effect of tryptophan on behaviour was discovered. Increasing doses of l-tryptophan were found to induce heightened startle response magnitude while reducing spontaneous locomotor activity. It was concluded that both the contraceptive effect and changes in behaviour, brought above after the administration of synthetic gonadal steroids, were caused by increased serotoninergic neuronal activity. It was suggested that these gonadel steroids induce changes in the equilibrium between the catecholaminergic end serotoninergic neuronal systems, causing the latter to predominate. The. hyperactivity syndrome, reported efter the concurrent administration of a monoamine oxidase inhibitor and either l-tryptophan or 5-hydroxytryptophan, was thought to be due to increased brain tryptemine levels, rather than the associated increase in brain 5-hydroxytryptamine levels,