Autoreceptor presynaptic control of dopamine release from striatum is lost at early stages of manganese poisoning.
Manganese (Mn) poisoning in man produces an early psychotic disorder that is later followed by a Parkinson-like syndrome. Since alterations in the brain DA system are thought to be involved, we assessed the presynaptic autoreceptor regulation of K(+)-evoked 3H-DA release from superfused striatal slices of mice treated i.p. with 5 mg Mn/kg weight/day for 2 and 8 weeks. Mn poisoning did not change basal and evoked DA release. In controls, 1 microM apomorphine (APO), a D2-like DA receptor agonist, produced an inhibition of K(+)-evoked 3H-DA release that was blocked by the D2-like DA receptor antagonist, S(-)-sulpiride (1 microM). Yet, APO lost its capacity to inhibit the K(+)-evoked 3H-DA release after 2 weeks of Mn poisoning. After 8 weeks of Mn poisoning, APO was again able to reduce K(+)-evoked 3H-DA release. MK-801 (0.3 microM), a NMDA-glutamate receptor antagonist, could restore APO inhibitory control on DA release lost at week 2 of Mn poisoning. These findings suggest a NMDA-glutamate-receptor-mediated loss of autoreceptor presynaptic control of striatal DA release at early Mn poisoning.
Cuesta de Di Zio
M C
MC
Section of Neurochemistry, School of Medicine, Universidad del Zulia, Maracaibo, Venezuela.
Gómez
G
G
Bonilla
E
E
Suarez-Roca
H
H
D000818:Animals; D017660:Autoreceptors / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D008345:Manganese / Q000378:metabolism; D020149:Manganese Poisoning; D051379:Mice; D017729:Presynaptic Terminals / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D017660:Autoreceptors; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D008345:Manganese; D004298:Dopamine