Intensification of central catecholaminergic and serotonergic processes by the hypothalamic factors MIF and TRF and by angiotensin II

Abstract

The present work deals with the action of MIF (melanocyte stimulating hormone release-inhibiting factor), TRF (thyrotropin releasing factor), and angiotensin II on the behavioral effects of L-DOPA and of D,L-5-hydroxytryptophan (5-HT) in mice. The influence of MIF and TRF on the antagonistic effect of L-DOPA of harmine tremors in rabbits was also studied. MIF and TRF, injected i.p., intensify the effects of L-DOPA in mice. The minimal dose of MIF required to induce a +3 response is 0.1 μg/kg; TRF is active at 500 μg/kg. When MIF or TRF are injected into the brain, potentiation of L-DOPA is obtained with exceedingly small quantities of MIF (0.1 pg); the effective dose of TRF is 1 μg. The behavioral effects of 5-HTP are potentiated by TRF only, at doses of 0.1 μg/kg, i.p. When TRF is administered intracerebrally, the active dose per mouse is 0.1 ng. Harmine (5 mg/kg i.v.) induces, in the rabbit, sustained whole body tremors; if L-DOPA (5 mg/kg) is administered i.v. at the peak of the harmine effect, the tremors subside. When the rabbit is pretreated with MIF, administered i.p. 1–2 hr before harmine, in doses devoid of an antitremor effect per se (10 μg/kg), the L-DOPA antagonism appears at lower doses. Also dopamine (5–10 mg/kg i.v.) proved effective in abating harmine tremors; previous treatment with MIF (50 μg/kg) potentiated the antagonistic effect of dopamine. According to the prevailing theories on the mechanism of neurotransmission, some hypothesis will be discussed to explain the observed potentiation: impaired uptake, impaired degradation, interference with the turnover of the bioamines, supersensitivity of the receptors.