Intensification of central catecholaminergin and serotonergic processes by the hypothalamic factors MIF and TRF and...

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-hydroxytrytophan (5-HTP) 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 microgram/kg; TRF is active at 500 micrograms/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 microgram. The behavioral effects of 5-HTP are potentiated by TRF only, at doses of 0.1 microgram/kg, i.p. When TRF is administered intracerebrally, the active dose per mouse is 0.1 ng. Harmine (5 mg/kg i.v.) induced, in the rabbit, sustained whole body tremors; if L-DOPA (5 mg/kg) is administered i.v. at the peak of the harmine effect, tremors subside. When the rabbit is pretreated with MIF administered i.p. 1 -2 hr before harmine, in doses devoid of an antitumor effect per se (10 micrograms/kg), the L-DOPA antagonism appears at lower dose. Also dopamine (5-10 mg/kg i,v.) proved effective in abating harmine tremors; previous treatment with MIF (50 micrograms/kg) potentiated the antagonistic effect of dopamine. According to the prevailing theories on the mechanism of neurotransmission, some hypotheses will be discussed to explain the observed potentiation: impaired uptake, impaired degradation, interference with the turnover of the boiamines, supersensitivity of the receptors.