Mechanism of the hypothermic effect of MPP+ administered centrally in mice.
The neurotoxin methyl phenyl pyridinium (MPP+) was administered intracerebroventricularly (i.c.v.) to mice. From the 1.25 microg dose per mouse, MPP+ elicited a dose-dependent hypothermic effect from doses as low as 1.25 microg per mouse. The minimal lethal dose was determined to be between 17.5 and 20 microg per mouse. The hypothermia induced by 2.5 microg MPP+ was unaffected by pretreatment with propranolol (8 mg/kg, i.p.), scopolamine (5 mg/kg, s.c.) and haloperidol (250 microg/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 microg, 8 days before testing with MPP+ 2.5 microg), 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 microg, 8 days before testing with 50 microg 6 OHDA) there was no modification in the hypothermic effect of 6 OHDA (50 microg). 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 alpha2 adrenoreceptors. In contrast, this agent in the present experimental conditions, does not destroy NE neurons in opposition to its action on DA neurons.
Drouet
I
I
Unité de Neuropsychopharmacologie expérimentale (CNRS URA 1969), Institut Féderatif de Recherche Multidisciplinaire sur les Peptides, Faculté de Medecine et Pharmacie de Rouen, Saint Etienne du Rouvray, France.
Suaudeau
C
C
Dourmap
N
N
Costentin
J
J
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007035:Hypothermia / Q000139:chemically induced*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D016627:Oxidopamine / Q000494:pharmacology
D015259:Dopamine Agents; D016627:Oxidopamine; D015655:1-Methyl-4-phenylpyridinium