Mechanism of the hypothermic effect of MPP + administered centrally in mice

Abstract

The neurotoxin methyl phenyl pyridinium (MPP +) was administered intracerebroventricularly (i.c.v.) to mice. From the 1.25 μg dose per mouse, MPP + elicited a dose-dependent hypothermic effect from doses as low as 1.25 μg per mouse. The minimal lethal dose was determined to be between 17.5 and 20 μg per mouse. The hypothermia induced by 2.5 μg MPP + was unaffected by pretreatment with propranolol (8 mg/kg, i.p.), scopolamine (5 mg/kg, s.c.) and haloperidol (250 μg/kg, i.p.). It was decreased by yohimbine (4 mg/kg, s.c.), idazoxan (5 mg/kg, s.c.) and desipramine (20 mg/kg, i.p.). In mice injected i.c.v. with 6 hydroxydopamine (50 μg, 8 days before testing with MPP + 2.5 μg), a significant reduction in the hypothermic effect of MPP + was observed. A similar 6 OHDA injection has been shown previously to reduce by about 40% the DA striatal content of DA and by about 70% the hypothalamic content of NE. On the contrary, in mice injected with MPP + (17.5 μg, 8 days before testing with 50 μg 6 OHDA) there was no modification in the hypothermic effect of 6 OHDA (50 μg). This injection of MPP + reduced by about 40% the striatal content of DA but did not affect the hypothalamic content of NE. It is concluded that MPP + decreases body temperature, at least in part, by acting as an indirect NE agonist, which stimulates α2 adrenoreceptors. In contrast, this agent in the present experimental conditions, does not destroy NE neurons in opposition to its action on DA neurons.