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Effects of ceruletide on the dopamine receptor-adenylate cyclase system in striatum and frontal cortex of rats chronically treated with haloperidol

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Abstract

Chronic treatment of rats with haloperidol decanoate (30 mg/kg and 100 mg/kg IM every 4 weeks for 52 weeks) increased [3H] SCH 23390 binding in striatal membranes by 25% and 50% and in frontal cortical membranes by 56% and 125% in 30 and 100 mg/kg haloperidol treatment groups, respectively. These increases in [3H] SCH 23390 binding to the membranes were restored to control levels after ceruletide treatment (100 µg/kg IP twice a day for 5 days). [3H] Spiperone binding to the rat striatal and cortical membranes also increased after chronic haloperidol treatment (by 66% and 99% in striatal membranes and by 27% and 62% in cortical membranes in the 30 and 100 mg/kg haloperidol treatment groups, respectively). Administration of ceruletide to haloperidol-treated rats reduced the increased [3H] spiperone binding to the cortical membranes toward the control level, but ceruletide was not effective in reducing the haloperidol-induced increase of [3H] spiperone binding to the striatal membranes. Activation of adenylate cyclase by dopamine (1 µM or 100 µM) or Gpp(NH)p (1 µM) was reduced in striatal and cortical membranes from haloperidol-treated rats. Ceruletide restored the lowered level of dopamine-stimulated or Gpp(NH)p-stimulated adenylate cyclase activity in the membranes from haloperidol-treated rats to control levels. These findings indicate that systemically administered ceruletide is capable of reversing alterations in D1 dopamine receptor/D1 dopamine receptor coupling to adenylate cyclase in striatum and frontal cortex induced by chronic treatment of rats with haloperidol decanoate.

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Authors and Affiliations

  1. Department of Neuropsychiatry, Sapporo Medical College, South-1, West-16, Chuo-ku, 060, Sapporo, Japan

    Yuko Hatta & Toshikazu Saito

  2. Department of Pharmacology, Sapporo Medical College, South-1, West-16, Chuo-ku, 060, Sapporo, Japan

    Shinichi Hatta

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  1. Yuko Hatta
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Hatta, Y., Hatta, S. & Saito, T. Effects of ceruletide on the dopamine receptor-adenylate cyclase system in striatum and frontal cortex of rats chronically treated with haloperidol. Psychopharmacology 110, 383–389 (1993). https://doi.org/10.1007/BF02244642

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  • DOI: https://doi.org/10.1007/BF02244642

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