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Journal of Pharmacology and Experimental Therapeutics

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OtherNEUROPHARMACOLOGY

Repeated Daily Cocaine Alters Subsequent Cocaine-induced Increase of Extracellular Dopamine in the Medial Prefrontal Cortex

Barbara A. Sorg, Debra L. Davidson, Peter W. Kalivas and Balakrishna M. Prasad
Journal of Pharmacology and Experimental Therapeutics April 1997, 281 (1) 54-61;
Barbara A. Sorg
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Debra L. Davidson
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Peter W. Kalivas
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Balakrishna M. Prasad
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Abstract

Male Sprague-Dawley rats that were naive or that had been treated with five daily saline or cocaine injections (15 mg/kg i.p.) were subsequently challenged with an injection of cocaine, and extracellular dopamine content in the medial prefrontal cortex (mPFC) was measured using in vivo microdialysis. Cocaine challenge increased extracellular dopamine levels from base line in all three groups of rats, but the augmentation was significantly reduced in the cocaine-pretreated group, compared with the saline-pretreated group. In contrast, mPFC dopamine levels were not different among groups after challenge with systemic d-amphetamine. To test whether repeated cocaine treatment led to altered releasability of dopamine from mPFC terminals, challenge with KCl (10, 30 or 100 mM) ord-amphetamine (3, 30 or 300 μM) was madevia infusion through the dialysis probe into the mPFC. No differences in dopamine levels were found between treatment groups for either drug at any dose. To determine whether the effects of cocaine were mediated by local actions within mPFC dopamine terminals, a cocaine challenge was administered through the microdialysis probe (1, 10 or 100 μM). In contrast to the systemic cocaine challenge, local infusion of cocaine elicited a significant increase in daily cocaine-pretreated rats, compared with saline-pretreated controls, at the lowest dose tested, with no differences at the higher two doses. In summary, daily cocaine-pretreated rats demonstrated a suppressed mPFC dopamine response to subsequent systemic, but not local, cocaine challenge. The results suggest that this apparent tolerance is not due to altered releasability of dopamine from mPFC terminals and may rely on altered afferent regulation of mesocortical dopamine neurons.

Footnotes

  • Send reprint requests to: Barbara A. Sorg, Program in Neuroscience, Department of VCAPP, Washington State University, Pullman, WA 99164-6520.

  • ↵1 This work was supported by United States Public Health Service Grants DA08212 (B.A.S.), DA03906 and MH40817 and Research Career Development Award DA00153 (P.W.K.).

  • Abbreviations:
    ANOVA
    analysis of variance
    CSF
    cerebrospinal fluid
    EAA
    excitatory amino acid
    mPFC
    medial prefrontal cortex
    VTA
    ventral tegmental area
    • Received January 17, 1996.
    • Accepted December 9, 1996.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 281, Issue 1
1 Apr 1997
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OtherNEUROPHARMACOLOGY

Repeated Daily Cocaine Alters Subsequent Cocaine-induced Increase of Extracellular Dopamine in the Medial Prefrontal Cortex

Barbara A. Sorg, Debra L. Davidson, Peter W. Kalivas and Balakrishna M. Prasad
Journal of Pharmacology and Experimental Therapeutics April 1, 1997, 281 (1) 54-61;

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OtherNEUROPHARMACOLOGY

Repeated Daily Cocaine Alters Subsequent Cocaine-induced Increase of Extracellular Dopamine in the Medial Prefrontal Cortex

Barbara A. Sorg, Debra L. Davidson, Peter W. Kalivas and Balakrishna M. Prasad
Journal of Pharmacology and Experimental Therapeutics April 1, 1997, 281 (1) 54-61;
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