ＴＲＨ類縁体（ＤＮ‐１４１７）　Ｒｅｓｅｒｐｉｎｅに対する脳内グルコース利用率および脳内モノアミンにおけるきっ抗作用

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  • A TRH analog (DN-1417). Antagonistic effects on reserpine-induced decreases in local cerebral glucose utilization and cerebral monoamine levels.
  • TRH ルイエンタイ DN-1417 Reserpine ニ タイスル ノウナ
  • Antagonistic effects on reserpine-induced decreases in local cerebral glucose utilization and cerebral monoamine levels

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抄録

Thyrotropin-releasing hormone (TRH) and its analog, DN-1417 (γ-butyrolactone-γ-carbonyl-L-histidyl-L-prolinamide citrate), significantly antagonized against reserpine-induced reduction of the spontaneous motor activity and the electroconvulsive threshold in mice. To search for sites of action and mechanisms, effects of DN-1417 on reserpine in local cerebral glucose utilization (LCGU) and cerebral monoamine levels were also investigated in rats. Reserpine (2 mg/kg, i.p., 24 hr pretreatment) reduced LCGU and the levels of cerebral monoamine in all the brain regions. DN-1417 (5 mg/kg, i.v.) significantly reversed the reduction of LCGU induced by reserpine in the thalamus dorsomedial nucleus, mamillary body, septal nucleus, caudate-putamen and nucleus accumbens. The effects of DN-1417 were completely abolished by pretreatment with a dopaminergic (DA) and a serotonergic (5-HT) receptor blocker, pimozide (1 mg/kg) and methysergide (5 mg/kg), respectively. DN-1417 (20 mg/kg, i.p.) reversed 5-HT level in the hypothalamus depleted by reserpine. These results suggest that the antagonistic effects of DN-1417 against reserpine-induced reduction of the locomotor activity and the electroconvulsive threshold seem to be mediated by DA and 5-HT-ergic activations mainly in the nucleus accumbens and hypothalamus, respectively.

収録刊行物

  • 日本薬理学雑誌

    日本薬理学雑誌 85 (5), 315-326, 1985

    公益社団法人 日本薬理学会

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