心臓型脂肪酸結合タンパク質による中枢ドパミン神経活動の調節

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  • Regulation of Dopaminergic Neuronal Activity by Heart-type Fatty Acid Binding Protein in the Brain
  • シンゾウガタ シボウサン ケツゴウ タンパクシツ ニ ヨル チュウスウ ドパミン シンケイ カツドウ ノ チョウセツ

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  Haloperidol as a potent dopamine D2 receptor (D2R) antagonist was a major tranquilizer to treat schizophrenia patients. However, the D2R blocking action in dorsal striatum is thought to cause extrapyramidal symptoms as adverse effects. However, the pathophysiological mechanism underlying extrapramidal symptoms induced by chronic treatment of haloperidol remains unclear. We recently found that lacking of heart-type fatty acid binding protein (H-FABP) in the brain aggravate catalepsy behavior induced by haloperidol. Here, we examined neuronal mechanism of augmentation of haloperidol-induced catalepsy in H-FABP null mice. Notably, catalepsy induced by haloperidol, a D2 antagonist, is augmented, whereas catalepsy induced by SCH23390, a D1 antagonist, was not affected in H-FABP null mice. Interestingly, haloperidol-induced acetylcholine (ACh) release in the dorsal striatum was markedly enhanced in H-FABP null mice compared to wild mice. We also defined the co-localization of D2R with H-FABP in the ACh interneurons in the striatum. Taken together, H-FABP regulates dopaminergic neuronal activity through interaction with D2R in rodent brain. The increased ACh release in the striatum accounts for haloperidol-induced catalepsy.<br>

収録刊行物

  • 薬学雑誌

    薬学雑誌 131 (4), 497-501, 2011-04-01

    公益社団法人 日本薬学会

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