Investigation of cocaine-induced changes in opioid receptors using selective monoamine uptake inhibitors

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Abstract

Psychomotor stimulants are known to interact behaviorally and biochemically with opioids. Chronic cocaine has been shown to increase μ-opioid receptor density in the rat nucleus accumbens. To investigate the mechanism by which continuous cocaine administration alters opioid receptors, the effects of selective monoamine uptake inhibitors on [3H]DAMGO binding were examined. Doses were selected based on a ratio of known affinities for the respective transporters, as compared to cocaine. GBR 12909 (30 mg/kg/day), fluoxetine (1.0 mg/kg/day), or nisoxetine (0.1 mg/kg/day) were continuously infused for seven days via osmotic minipumps into male Sprague-Dawley rats. Twenty-four hours after pump removal the rats were sacrificed and their caudate putamen and nucleus accumbens dissected on ice for immediate assay. At the doses tested, neither GBR 12909, fluoxetine, nor nisoxetine produced significant effects on Kd or Bmax values in the caudate putamen or nucleus accumbens. These preliminary results suggest that cocaine may not exert its opioid altering effects through any of the individual monoamine systems, but may require the combination of two, or perhaps, all three systems. Further examination of the effects of these compounds on opioid receptor function are underway.

Original languageEnglish
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996
Externally publishedYes

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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