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 H-3-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 mu M apomorphine (APO), a D-2-like DA receptor agonist, produced an inhibition of K+-evoked H-3-DA release that was blocked by the D-2-like DA receptor antagonist, S(-)-sulpiride (1 mu M). Yet, APO lost its capacity to inhibit the K+-evoked H-3-DA release after 2 weeks of Mn poisoning. After 8 weeks of Mn poisoning, APO was again able to reduce K+-evoked H-3-DA release. MK-801 (0.3 mu M), 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.