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Development of behavioral tolerance and reverse tolerance during withdrawal periods after chronic psychostimulant treatment

Research Project

Project/Area Number 06670964
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionYamaguchi University

Principal Investigator

USHIJIMA Itsuko  Department of Neuropsychiatry, Assistant Professor, 医学部, 助手 (30168679)

Co-Investigator(Kenkyū-buntansha) YAMADA Michio  Department of Neuropsychiatry, Professor, 医学部, 教授 (00034942)
MIZUKI Yasushi  Department of Neuropsychiatry, Associate Professor, 医学部, 助教授 (00080721)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
KeywordsCocaine / Methamphetamine / Chronic treatment / Withdrawal period / SCH23390 catalepsy / Haloperidol-catalepsy / Pertussis toxin / Gi-protein ADP-ribosylation / Chronic cocaine treatment / Dopamine antagonists / Coadministration / Catalepsy / Withdrawal period / Pertussis toxin / Gi-protein ADP-ribosylation / Cocaine / Methamphetamine / Chronic treatment / SCH23390 catalepsy / Haloperidol catalepsy / Tolerance / Reverse tolerance / Dopamine system
Research Abstract

Chronic treatment with the indirect dopamine agonists cocaine and methamphetamine, caused supersinsitivity of D_1 receptors (decrease of SCH23390 catalepsy) and subsensitivity of D_2 receptors (increase of haloperidol catalepsy) during the early withdrawal period in mice. This decrease in cataleptic response to SCH23390 after exposure to cocaine could be interpreted as development of supersensitivity of dopamine D_1 receptors, which corresponds to the development of sensitization to cocaine. The increase in haloperidol catalepsy after exposure to cocaine may represent a state of subsensitivity of dopamine D_2 receptors, which corresponds with the development of tolerance to cocaine. This would indicate that the D_1 receptor may be mainly involved in psychostimulant-induced sensitization, which in man is manifested as psychostimulant-induced psychosis and schizophrenia-like symptoms. The chronic cocaine pretreatment caused sub-sensitivity of D_1 receptors (an increase in SCH-23390 catal … More epsy) after a longer period of withdrawal. It was apparent that the longer the period and the higher the dose of pretreatment with cocaine, the less were the alterations in initial responses and the greater were the alterations in subsequent responses to the dopamine D_1 receptor antagonists. Coadministration of either SCH23390 or haloperidol prevented the development of D_1 receptor supersinsitivity and D_2 receptor subsensitivity induced during early with- drawal periods. However, the subsensitive effect of dopamine D_1 receptors during long-term withdrawal period was rather aggravated by coadministration of SCH-23390 or haloperidol, suggesting that dopamine D_1 or D_2 receptor antagonist is not effective as an antipsychotic drug in the withdrawal periods. Furthermore, the decreasing effect of chronic cocaine on SCH23390 catalepsy was inhibited by a single pretreatment with pertussis toxin which catalyze ADP-ribosylation of G_i-proteins, whereas the increasing effect of that on haloperidol catalepsy was enhanced. These results suggest that there may be an interrelationship between D_2 receptor subsensitivity, but not D_1 receptor supersensitivity and, during early withdrawal periods and Gi-protein ADP-ribosylation. Less

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] I. Ushijima, Y. Mizuki M. Yamada: "Development of tolerance and reverse tolerance ot haloperidol-and SCH23390-induced cataleptic effects during withdrawal periods after long-term treatment" Pharmacol. Biochem. Behav.50 (2). 259-264 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I. Ushijima, Y. Mizuki M. Yamada: "Alteration of cataleptic responses induced by dopamine receptor antagonists after chronic cocaine administration in mice" Europ. J. Pharmacol.285 (1). 55-59 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y. Mizuki, I. Ushijima M. Yamada: "Effects of chronic methamphetamine on SCH23390-or haloperidol-induced catalepsy, and effects of coadministration of SCH23390 or haloperidol in mice" Pharmacol. Biochem. Behav.53 (2). 437-440 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] ITSUKO USHIJIMA,YASUSHI MIZUKI,MICHIO YAMADA: "Development of tolerance and reverse tolerance to haloperidol- and SCH23390-induced cataleptic effects during withdrawal periods after long-term treatment" Pharmacol.Biochem.Behav.50(2). 259-264 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] ITSUKO USHIJIMA,YASUSHI MIZUKI,MICHIO YAMADA: "Alteration of cataleptic responses induced by dopamine receptor antagonists after chronic cocaine administration in mice" Europ.J.Pharmacol.285(1). 55-59 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] YASUSHI MIZUKI,ITSUKO USHIJIMA,MICHIO YAMADA: "Effects of chronic methamphetamine on SCH23390-or haloperidol-induced catalepsy, and effects of coadministration of SCH23390 or haloperidol in mice" Pharmacol.Biochem.Behav.53(2). 437-440 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] I.Ushijima,Y.Mizuki and M.Yamada: "Development of tolerance and reverse tolerance to haloperidol-and SCH23390-induced cataleptic effects during withdrawal periods after long-term treatment" Pharmacol.Biochem.Behav.50(2). 259-264 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] I.Ushijima,Y.Mizuki and M.Yamada: "Alteration of cataleptic responses induced by dopamine receptor antagonists after chronic cocaine administration in mice" Europ.J.Pharmacol.285(1). 55-59 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y.Mizuki,I.Ushijima and M.Yamada: "Effects of chronic methamphetamine on SCH23390- or haloperidol-induced catalepsy,and effects of coadministration of SCH23390 or haloperidol in mice" Pharmacol.Biochem.Behav.53(2). 437-440 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] I.Ushijima,Y.Misuki,M.Yamada: "Development of tolerance and reverse tolerance to haloperidol-and SCH23390 induced cataleptic effects during withdrawal periods arter long term treatment" Pharmacol Biochem Behav.50. (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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