title: Intensification of central catecholaminergin 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-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.
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006247:Harmine / Q000037:antagonists & inhibitors; D007267:Injections; D007980:Levodopa / Q000494:pharmacology; D009075:MSH Release-Inhibiting Hormone / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010293:Pargyline / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism*; D013268:Stimulation, Chemical; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D014202:Tremor / Q000139:chemically induced
chemical_list: D002395:Catecholamines; D000804:Angiotensin II; D012701:Serotonin; D007980:Levodopa; D006247:Harmine; D013973:Thyrotropin-Releasing Hormone; D009075:MSH Release-Inhibiting Hormone; D010293:Pargyline; D006916:5-Hydroxytryptophan