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Research ArticleNEUROPHARMACOLOGY

Dopamine D1 Receptor Activation in the Medial Prefrontal Cortex Prevents the Expression of Cocaine Sensitization

Barbara A. Sorg, Na Li and Wei-Ran Wu
Journal of Pharmacology and Experimental Therapeutics May 2001, 297 (2) 501-508;
Barbara A. Sorg
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Na Li
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Wei-Ran Wu
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Abstract

This study examined whether microinjection of the full D1 agonist, SKF 81297, or the D1 antagonist, SCH 23390, into the medial prefrontal cortex (mPFC) would alter the expression phase of cocaine sensitization. Male Sprague-Dawley rats were administered saline or cocaine (15 mg/kg, i.p.) once per day for seven consecutive days. After 8 to 17 days withdrawal, rats received a bilateral intra-mPFC microinjection of SKF 81297: either 0, 0.03, 0.1, or 0.3 μg/side; SCH 23390: either 0, 0.1, 0.3, or 1.0 μg/side; or a combination of 0.1 μg of SKF 81297 + 0.3 μg of SCH 23390, followed by an i.p. saline or cocaine (15 mg/kg, i.p.) injection. In naı̈ve rats, vertical activity was elevated by the two lower doses of SKF 81297. A similar enhancement of cocaine-induced activity was observed in daily saline rats at the highest dose tested. In contrast, SKF 81297 suppressed the expression of sensitization to cocaine. This blockade of sensitization was prevented by coinfusion of SCH 23390. Infusion of SCH 23390 alone into the mPFC in daily saline and cocaine-pretreated rats demonstrated a suppression of cocaine-induced locomotion in daily saline-pretreated rats after the highest dose, but a slight augmentation of activity after the lowest dose in daily cocaine-pretreated rats. These results demonstrate a contribution by mPFC D1 receptors in the expression of cocaine sensitization and further suggest that the effects of D1 receptor activation in the mPFC occur in opposite directions in daily saline versus daily cocaine-pretreated rats.

Footnotes

  • Send reprint requests to: Dr. Barbara A. Sorg, Alcohol and Drug Abuse Program, Dept. of VCAPP, Stadium Way, Wegner Hall, Rm. 205, Washington State University, Pullman, WA 99164-6520. E-mail: barbsorg{at}vetmed.wsu.edu

  • This work was supported by U.S. Public Health Service Grant DA 11787 (to B.A.S.).

  • Abbreviations:
    mPFC
    medial prefrontal cortex
    AMPH
    amphetamine
    ANOVA
    analysis of variance
    EAA
    excitatory amino acid
    GABA
    γ-aminobutyric acid
    VTA
    ventral tegmental area
    • Received October 13, 2000.
    • Accepted January 5, 2001.
  • U.S. Government
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Journal of Pharmacology and Experimental Therapeutics: 297 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 297, Issue 2
1 May 2001
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Research ArticleNEUROPHARMACOLOGY

Dopamine D1 Receptor Activation in the Medial Prefrontal Cortex Prevents the Expression of Cocaine Sensitization

Barbara A. Sorg, Na Li and Wei-Ran Wu
Journal of Pharmacology and Experimental Therapeutics May 1, 2001, 297 (2) 501-508;

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Research ArticleNEUROPHARMACOLOGY

Dopamine D1 Receptor Activation in the Medial Prefrontal Cortex Prevents the Expression of Cocaine Sensitization

Barbara A. Sorg, Na Li and Wei-Ran Wu
Journal of Pharmacology and Experimental Therapeutics May 1, 2001, 297 (2) 501-508;
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