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Research ArticleArticle

Effects of Antipsychotic Drugs on Extracellular Dopamine Levels in Rat Medial Prefrontal Cortex and Nucleus Accumbens

Toshihide Kuroki, Herbert Y. Meltzer and Junji Ichikawa
Journal of Pharmacology and Experimental Therapeutics February 1999, 288 (2) 774-781;
Toshihide Kuroki
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Herbert Y. Meltzer
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Junji Ichikawa
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Abstract

The present study was designed to compare the effects of typical and atypical antipsychotic drugs on extracellular dopamine (DA) levels in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAC), using in vivo microdialysis with dual probe implantation in awake, freely moving rats. Amperozide (2 and 10 mg/kg), clozapine (5 and 20 mg/kg), and olanzapine (10 mg/kg), all of which are atypical antipsychotics, produced greater increases in extracellular DA levels in the mPFC than in the NAC. Olanzapine (1 mg/kg), risperidone (0.1 and 1 mg/kg), also an atypical antipsychotic, andS-(−)-sulpiride (25 mg/kg), a typical antipsychotic, produced comparable increases in extracellular DA levels in the mPFC and the NAC. S-(−)-sulpiride (10 mg/kg) and haloperidol (0.1 and 1 mg/kg), another typical antipsychotic, significantly increased extracellular DA levels in the NAC but not in the mPFC. The effects of the six antipsychotic drugs to increase extracellular DA levels in the mPFC relative to those in the NAC was positively correlated with the difference between their pKi values for serotonin (5-hydroxytryptamine, 5-HT2A) and DA-D2receptors and was inversely correlated to their pKi values for D2 or D3 receptors, but was not for 5-HT2A receptors alone. These results are consistent with the hypothesis that the ability of antipsychotic drugs to produce a greater increase in prefrontal compared with NAC extracellular DA levels may be related, in part, to weak D2 and D3 receptor affinity relative to 5-HT2Areceptor antagonism.

Footnotes

  • Send reprint requests to: Toshihide Kuroki, M.D., Ph.D., Department of Psychiatry, Saga Medical School, Nabeshima 5-1-1, Saga 849-8501, Japan. E-mail:kurokit{at}post.saga-med.ac.jp

  • ↵1 This work was supported in part by U.S. Public Health Services Grant MH 41684, Department of Veterans Affairs grant GCRC MO1RR00080, and the National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award grant, as well as grants from Elisabeth Severance Prentiss Foundation and Mr. Larry Freedman. Preliminary data from this study have been reported in abstract forms of the annual meetings of the Society for Neuroscience, 1995, and the Society of Biological Psychiatry, 1996.

  • Abbreviations:
    HAL
    haloperidol
    SUL
    S-(−)-sulpiride
    DA
    dopamine
    STR
    striatum
    NAC
    nucleus accumbens
    CLOZ
    clozapine
    APZ
    amperozide
    mPFC
    medial prefrontal cortex
    OLAN
    olanzapine
    RISP
    risperidone
    5-HT
    5-hydroxytryptamine
    AUC
    area under the curve
    VEH
    vehicle control
    • Received April 10, 1998.
    • Accepted September 14, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 2
1 Feb 1999
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Research ArticleArticle

Effects of Antipsychotic Drugs on Extracellular Dopamine Levels in Rat Medial Prefrontal Cortex and Nucleus Accumbens

Toshihide Kuroki, Herbert Y. Meltzer and Junji Ichikawa
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 774-781;

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Research ArticleArticle

Effects of Antipsychotic Drugs on Extracellular Dopamine Levels in Rat Medial Prefrontal Cortex and Nucleus Accumbens

Toshihide Kuroki, Herbert Y. Meltzer and Junji Ichikawa
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 774-781;
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