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Cocaine sensitization: modulation by dopamine D2 receptors.

Chad E Beyer1, Jeffery D Steketee

  • 1Department of Pharmacology and Therapeutics and School of Graduate Studies, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.

Cerebral Cortex (New York, N.Y. : 1991)
|April 16, 2002
PubMed
Summary

Activation of dopamine D(2)-like receptors in the medial prefrontal cortex (mPFC) blocks cocaine-induced behavioral sensitization. This suggests D(2)-like receptors in the mPFC are crucial for developing enduring changes related to cocaine addiction.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Science

Background:

  • Repeated cocaine use leads to increased locomotor activity, a phenomenon known as behavioral sensitization.
  • The medial prefrontal cortex (mPFC) plays a role in mediating these sensitized behaviors.
  • Dopamine receptors, specifically D(1)-like and D(2)-like subtypes, are implicated in drug addiction.

Purpose of the Study:

  • To investigate the role of dopamine D(1)-like and D(2)-like receptors in the mPFC in the initiation and expression of cocaine-induced behavioral sensitization.
  • To determine if activating these receptors affects neurochemical changes associated with cocaine sensitization.

Main Methods:

  • Animals received intra-mPFC injections of D(1)-like (SKF 81297) or D(2)-like (quinpirole) receptor agonists before cocaine administration.

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  • Behavioral sensitization was assessed through locomotor activity tests after cocaine challenge.
  • In vivo microdialysis measured dopamine levels in the nucleus accumbens to assess neurochemical sensitization.

    • Main Results:

    • Intra-mPFC quinpirole administration blocked the initiation and attenuated the expression of cocaine-induced behavioral sensitization.
    • Intra-mPFC SKF 81297 did not affect the induction or expression of sensitization at the tested dose.
    • Quinpirole also blocked the initiation and blunted the expression of cocaine-induced neurochemical sensitization in the nucleus accumbens.

    Conclusions:

    • Activation of dopamine D(2)-like receptors in the mPFC is critical for the development of cocaine-induced behavioral and neurochemical sensitization.
    • These findings suggest that targeting D(2)-like receptors in the mPFC could be a potential therapeutic strategy for cocaine addiction.