CHANGES IN TRANSITION-METAL CONTENTS IN RAT-BRAIN REGIONS AFTER IN-VIVO QUINOLINATE INTRASTRIATAL ADMINISTRATION

Total copper and manganese contents were measured in five rat brain re gions 7 days after a unilateral striatal injection of quinolinic acid (QUIN, 240 nmol/1 mu l), an endogenous N-methyl-D-aspartate (NMDA) rec eptor agonist. Concentrations of both transition metals were evaluated in tissue of brain cortex, hippocampus, corpus striatum, midbrain and cerebellum of saline- and QUIN-treated rats using graphite furnace at omic absorption spectrophotometry. Increases in copper content were ob served after QUIN striatal injection in cerebellum, hippocampus, midbr ain and corpus striatum (37, 55,71 and 152% as compared against contro l values, respectively) but not in brain cortex. Manganese levels were found enhanced only in corpus striatum of QUIN-treated rats by 35% vs . control values, but not in all other brain regions analyzed. QUIN-in duced increases in regional copper content were partially prevented in hippocampus, midbrain and striatum (17, 57, and 23% vs. control, resp ectively) by pretreatment of rats with an NMDA receptor antagonist, di zocilpine (MK-801, 10 mg/kg, i.p.), administered 60 min before QUIN mi croinjection. The same protective effect of dizocilpine was observed a gainst. QUIN-induced enhancement of striatal manganese content (-0.45% vs. control). These findings resemble those changes observed in postm ortem Huntington's disease brains and suggest that alterations in regi onal content of copper, but not in manganese, may be a consequence of the spreading of QUIN-induced neurotoxic events into the striatal tiss ue to the neighboring regions of the brain, by action of QUIN on NMDA receptors.