Enhancement of Locomotor Activity and Catecholamine and 5-Hydroxytryptamine Metabolism by Thyrotropin Releasing Hormone

Abstract

I.p. administration of thyrotropin releasing hormone (TRH) twice daily for 10 days produced a dose- and time-dependent rise in spontaneous locomotor activity of young rats. A significant increase in the levels of cerebrocortical 5-hydroxytryptamine (5-HT) and dopamine (DA) also observed in animals treated with varying amounts of TRH (2, 4 and 8 mg/kg per day). The concentration of these amines was elevated after a 10- or 15-day treatment with a 4 mg/kg daily dose of TRH, but no change was observed in rats given the hormone for only 5 days. The amount of 5-hydroxyindoleacetic acid (5-HIAA) rose after a 15-day treatment; however, no significant change was seen in norepinephrine (NE) levels of any of the groups examined. The activity of brain stem tyrosine hydroxylase (TH) showed a dose-dependent increase in rats chronically treated with TRH. Although there was a significant rise in brain stem tryptophan hydroxylase (TPH) activity as well, the response was neither time- nor dose-dependent. A single injection of 200 .mu.Ci of 131I at birth induced hypothyroidism, which was accompanied by decreased brain stem TH activity. 5-HIAA levels were markedly enhanced in hypothyroid rats. These changes were partially reversed after a 10-day treatment with 4 mg/kg daily dose of TRH. The data demonstrate that the rise in spontaneous locomotor activity following TRH administration in normal rats is related to altered catecholamine and possibly 5-HT metabolism brought about by this hormone. Since TRH treatment produced similar changes in the noradrenergic system of normal and hypothyroid rats, but not in the dopaminergic or 5-hydroxytryptaminergic systems, it is suggested that part of the central effects of TRH are independent of the pituitary-thyroid axis.