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502 Effect of haloperidol on cytochrome oxidase activity in the substantia nigra pars reticulata : histochemical study in rat brain
S69
5. Monoamines
501
INVOLVEMENT OF GLUTAMATE IN L-DOPA NEUROTOXICII-Y IN CULTURED STRIATAL NEURONS. TAKEHIKO MAEDA’. AKINORI AKAIKE’. MUTSUAKI UEDA*. MASAMICHI SATOH*, YOSHIOGOSHIMA3AND3MISU3,DeDzof’Pharmacol.2Mol. Pull.. Fat. ofeut. Sci Kyoto Univ.. Kvoto.31&pt. of P-01.. Yokohama City Univ. Sch. of Me236. &@w This study was performed to examine the mechanism underlying L-dopa-induced neurotoxicity in striatal neurons. Primary cultures obtained from fetal rat striatum (17-19 days gestation) were used for experiments. In 10 days in culture (DIC), marked cell death was induced by L-dopa (30-1000 pM, 6-24 hr) in concentration- and time-dependent manners. L-dopa (30300 l.tM) increased glutamate release from striatal cultures in a concentration-dependent manner. L-dopa cytotoxicity was ameliorated by a simultaneous application of MK-801 (10 PM), a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and CNQX (10 PM), a non-NMDA receptor antagonist. Furthetmom, Ca*+-removal or elevation of concentration of Mg*+ in the L-dopa-containing medium prevented L-dopa cytotoxicity. In contrast, neither NSD-1015 (20 l.tM), a dopa decarboxylase inhibitor, nor ascorbate (200 ttM), an anti-oxidant, affected L-dopa cytotoxicity. Ddopa (100 pM, 24 hr), an enantiomer of L-dopa, did not affect viability of 10 DIC cells though it induced cytotoxic effect on 3 DIC cells. These results suggest that L-dopa induces neurotoxicity in cultured striatal neurons by facilitating glutamate release via a recognition site for L-dopa itself.
502
EFFECT OF HALOPERIDOL ON CYTOCHROME OXIDASE ACTIVITY IN THE SUBSTANTIA NlGRA PARS RETICULATA : HISTOCHEMICAL STUDY IN RAT BRAIN. CHIHIRO YOKOYAMti AND YASUHIKO IBATAZIDept. of Anat.. Kawasaki Med. Sch., Matsushima, Kurashiki. 701-01, ZKvoto Pref. Univ. of Med.. Kawaramachi-Hirokoii, Kvoto 602. Japan. Functional activity of neurons is coupled with oxidative energy metabolism. A mitochondrial enzyme, cytochrome oxidase (CO) is the terminal enzyme in the electron transport chain of the oxidative phosphorylation, and an endogenous marker of local tissue metabolic activity. CO histochemistry could be detected the precise change of anatomical localization of CO activity under specific conditions. In the present study, we examined effect of subchronic haloperidol treatment (5 mg/Kg, 6 days) on CO activity in rat brain. CO histochemical staining was changed in the substantia nigra in the midbrain. In the control group, the substantia nigra pars reticulata (SNr) showed moderate CO activity and the staining of individual neurons was more intensive in lateral than medial SNr, while the substantia nigra pars compacta (SNc) showed only low CO activity without any distinctive cell bodies. After subchronic treatment of haloperidol, CO staining neurons in SNr tended to extend more medially and their number in SNr was increased. These results suggest a regional gradient in CO activities of neurons and the region-specific disinhibition caused by dopamine blockade in SNr.
5. Monoamines
501
INVOLVEMENT OF GLUTAMATE IN L-DOPA NEUROTOXICII-Y IN CULTURED STRIATAL NEURONS. TAKEHIKO MAEDA’. AKINORI AKAIKE’. MUTSUAKI UEDA*. MASAMICHI SATOH*, YOSHIOGOSHIMA3AND3MISU3,DeDzof’Pharmacol.2Mol. Pull.. Fat. ofeut. Sci Kyoto Univ.. Kvoto.31&pt. of P-01.. Yokohama City Univ. Sch. of Me236. &@w This study was performed to examine the mechanism underlying L-dopa-induced neurotoxicity in striatal neurons. Primary cultures obtained from fetal rat striatum (17-19 days gestation) were used for experiments. In 10 days in culture (DIC), marked cell death was induced by L-dopa (30-1000 pM, 6-24 hr) in concentration- and time-dependent manners. L-dopa (30300 l.tM) increased glutamate release from striatal cultures in a concentration-dependent manner. L-dopa cytotoxicity was ameliorated by a simultaneous application of MK-801 (10 PM), a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and CNQX (10 PM), a non-NMDA receptor antagonist. Furthetmom, Ca*+-removal or elevation of concentration of Mg*+ in the L-dopa-containing medium prevented L-dopa cytotoxicity. In contrast, neither NSD-1015 (20 l.tM), a dopa decarboxylase inhibitor, nor ascorbate (200 ttM), an anti-oxidant, affected L-dopa cytotoxicity. Ddopa (100 pM, 24 hr), an enantiomer of L-dopa, did not affect viability of 10 DIC cells though it induced cytotoxic effect on 3 DIC cells. These results suggest that L-dopa induces neurotoxicity in cultured striatal neurons by facilitating glutamate release via a recognition site for L-dopa itself.
502
EFFECT OF HALOPERIDOL ON CYTOCHROME OXIDASE ACTIVITY IN THE SUBSTANTIA NlGRA PARS RETICULATA : HISTOCHEMICAL STUDY IN RAT BRAIN. CHIHIRO YOKOYAMti AND YASUHIKO IBATAZIDept. of Anat.. Kawasaki Med. Sch., Matsushima, Kurashiki. 701-01, ZKvoto Pref. Univ. of Med.. Kawaramachi-Hirokoii, Kvoto 602. Japan. Functional activity of neurons is coupled with oxidative energy metabolism. A mitochondrial enzyme, cytochrome oxidase (CO) is the terminal enzyme in the electron transport chain of the oxidative phosphorylation, and an endogenous marker of local tissue metabolic activity. CO histochemistry could be detected the precise change of anatomical localization of CO activity under specific conditions. In the present study, we examined effect of subchronic haloperidol treatment (5 mg/Kg, 6 days) on CO activity in rat brain. CO histochemical staining was changed in the substantia nigra in the midbrain. In the control group, the substantia nigra pars reticulata (SNr) showed moderate CO activity and the staining of individual neurons was more intensive in lateral than medial SNr, while the substantia nigra pars compacta (SNc) showed only low CO activity without any distinctive cell bodies. After subchronic treatment of haloperidol, CO staining neurons in SNr tended to extend more medially and their number in SNr was increased. These results suggest a regional gradient in CO activities of neurons and the region-specific disinhibition caused by dopamine blockade in SNr.