Autoreceptor presynaptic control of dopamine release from striatum is lost at early stages of manganese poisoning.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Cuesta de Di Zio, MC; Gómez, G; Bonilla, E; Suarez-Roca, H

Published Date

  • January 1995

Published In

Volume / Issue

  • 56 / 22

Start / End Page

  • 1857 - 1864

PubMed ID

  • 7746094

Pubmed Central ID

  • 7746094

Electronic International Standard Serial Number (EISSN)

  • 1879-0631

International Standard Serial Number (ISSN)

  • 0024-3205

Digital Object Identifier (DOI)

  • 10.1016/0024-3205(95)00160-8

Language

  • eng