MECHANISM OF THE HYPOTHERMIC EFFECT OF MPP+ ADMINISTERED CENTRALLY INMICE

The neurotoxin methyl phenyl pyridinium (MPP+) was administered intrac erebroventricularly (i.c.v.) to mice. From the 1.25 mu g dose per mous e, MPP+ elicited a dose-dependent hypothermic effect from doses as low as 1.25 mu g per mouse. The minimal lethal dose was determined to be between 17.5 and 20 mu g per mouse. The hypothermia induced by 2.5 mu g MPP+ was unaffected by pretreatment with propranolol (8 mg/kg, i.p.) , scopolamine (5 mg/kg, s.c.) and haloperidol (250 mu g/kg, i.p.). It was decreased by yohimbine (4 mg/kg, s.c.), idazoxan (5 mg/kg, s.c.) a nd desipramine (20 mg/kg, i.p.). In mice injected i.c.v. with 6 hydrox ydopamine (50 mu g, 8 days before testing with MPP+ 2.5 mu g), a signi ficant reduction in the hypothermic effect of MPP+ was observed. A sim ilar 6 OHDA injection has been shown previously to reduce by about 40% the DA striatal content of DA and by about 70% the hypothalamic conte nt of NE. On the contrary, in mice injected with MPP+C(17.5 mu g, 8 da ys before testing with 50 mu g 6 OHDA) there was no modification in th e hypothermic effect of 6 OHDA (50 mu g). This injection of MPP+ reduc ed by about 40% the striatal content of DA but did not affect the hypo thalamic content of NE. It is concluded that MPP+ decreases body tempe rature, at least in part, by acting as an indirect NE agonist, which s timulates alpha 2 adrenoreceptors. In contrast, this agent in the pres ent experimental conditions, does not destroy NE neurons in opposition to its action on DA neurons. (C) 1997 Elsevier Science Ltd.