Roles of Monoamine Neurotransmitters in the Regulation of Hypothalamic-Pituitary-Adrenal Axis (HPA) (II) - Role of 5-H'ydroxytryptamine(Serotonin) in Controlling the Circadian Rhythmicity of Corticosterone in Rat

Various pharmacologic studies have supported a stimulatory role of brain serotonin neurons in the hypothalamic regulation of circadian rhythmicity of pituitary-adrenocortical system in rats. The serotonin precursors (Lvtryptophan and L-5-hydroxytryptophan) , direct acting serotonin agonist C5-Methoxy-N-N-dimethyltryptamine) and monoamine oxidase inhibitor (Pargyline) all elevate both morning and evening plasma corticosterone levels in rats. The elevation of plasma corticosterone by L-tryptophan (lOOmg/ kg) was potentiated by monoamine oxidase inhibitor, pargyline C70mg/kg). The elevation of plasma corticosterone by 5-hydroxytryptophan and 5-methoxy-N-N-dimethyl tryptamine showed a dose-related fashion both in the morning and in the evening. Serotonin synthesis inhibitor (Pv chlorophenyialanine) and serotonin neurotoxin(5,7-dihydroxy tryptamine) caused a fall in plasma corticosterone level. Daily injections of p-chlorophenylalanine (300 mg/kg/day) for 2 days raised the morning low and prevented the evening rise in plasma corticosterone. The evening rise in plasma corticosterone was restored by the injection of 5-hydroxytryptophan and 5-methoxy-N-N-dimethyltryptamine. There was a positive correlation between the concentrations of serotonin in the hypothalamus and the concentrations of plasma corticosterone caused by various pharmacologic manipulation. Thus, our studies suggested that brain serotoninergic neurons may play an important role in the regulation of the diurnal rhythmicity of adrenocortical function