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Related Experiment Videos

Withdrawal from continuous or intermittent cocaine administration: changes in D2 receptor function

G R King1, E H Ellinwood, C Silvia

  • 1Department of Psychiatry, Duke University Medical Center, Durham, North Carolina.

The Journal of Pharmacology and Experimental Therapeutics
|May 1, 1994
PubMed
Summary
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Continuous cocaine use leads to tolerance by increasing dopamine D2 autoreceptor sensitivity. Intermittent use does not cause this tolerance, though it decreases D2 receptor mRNA levels.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Addiction Research

Background:

  • Cocaine administration can lead to either sensitization or tolerance depending on the dosing regimen.
  • The role of dopamine D2 receptors in these differential effects remains unclear.

Purpose of the Study:

  • To investigate the functional status of dopamine (DA) D2 receptors following chronic intermittent versus continuous cocaine administration in rats.
  • To determine if alterations in D2 receptor function correlate with cocaine-induced tolerance or sensitization.

Main Methods:

  • Rats received either continuous or intermittent cocaine for 14 days, followed by a 7-day withdrawal period.
  • Behavioral responses to apomorphine, dopamine release in striatal slices, and D2 receptor binding and mRNA levels were assessed.

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Main Results:

  • Continuous cocaine administration induced D2 autoreceptor supersensitivity, evidenced by enhanced behavioral inhibition to apomorphine and altered dopamine release.
  • No changes in postsynaptic D2 receptor binding or mRNA were observed with continuous cocaine.
  • Intermittent cocaine did not show D2 autoreceptor subsensitivity but decreased D2 mRNA levels by 22%.

Conclusions:

  • The findings support the hypothesis that D2 autoreceptor supersensitivity is associated with the development of tolerance to cocaine after continuous administration.
  • Differential regulation of D2 autoreceptors versus postsynaptic receptors may underlie distinct behavioral outcomes of cocaine dosing patterns.