QUINOLINIC ACID NEUROTOXICITY - IN-VIVO INCREASED COPPER AND MANGANESE CONTENT IN RAT CORPUS STRIATUM AFTER QUINOLINATE INTRASTRIATAL INJECTION

Copper and manganese, two essential metals involved in physiological a nd physiopathological processes in the brain, were measured in corpora striata of rats 7 days after intrastriatal injection of quinolinic ac id (QUIN, 240 nmol/l mu l), an N-methyl-D-aspartate (NMDA) receptor ag onist with toxic activity. Seven days after QUIN administration, coppe r and manganese contents were assessed by graphite furnace atomic abso rption spectrophotometry. Total copper content was increased by 152% i n QUIN-treated rats (18.74 +/- 2.05 mu g/g) as compared to control ani mals (7.44 +/- 1.15 mu g/g), whereas manganese striatal levels were en hanced by 35% (0.30 +/- 0.02 mu g/g) vs. control values (0.22 +/- 0.02 mu g/g). Quinolinate-induced striatal increase in copper and manganes e levels were prevented by 23% (9.18 +/- 1.43 mu g/g) and -0.45% (0.22 +/- 0.03 mu g/g) vs. control values, respectively, in rats pretreated with an NMDA receptor antagonist, dizocilpine (MK-801, 10 mg/kg, i.p. ), 60 min before QUIN administration. As an index of QUIN neurotoxicit y, striatal GABA levels were also measured 7 days after QUIN injection . GABA content was decreased by - 55% in QUIN-lesioned rats (96.37 +/- 8.92 mu g/g), whereas MK-801 was able to block QUIN-induced GABA depl etion by 2% (219.37 +/- 10.60) vs. control values (214.2 +/- 21.88 mu g/g). These findings suggest that increased concentrations of transiti on metals can be mediated by selective overactivation of NMDA receptor s and might be a consequence of neural loss as well as glial response to damage.