The cocaine-like behavioral effects of meperidine are mediated by activity at the dopamine transporter

Sari Izenwasser, Amy Hauck Newman, Brian M. Cox, Jonathan L. Katz

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Meperidine has atypical opioid receptor agonist effects and shares some structural features with the phenyltropane (WIN) analogs of cocaine. In combination with 0.1 mg/kg naltrexone, meperidine produced cocaine-like discriminative stimulus effects in monkeys, whereas morphine was inactive. Both cocaine and meperidine inhibited [3H]dopamine uptake in chopped rat caudate putamen with comparable potencies; meperidine differed from cocaine in that its effects could be characterized as having predominantly a single high-affinity component. Morphine was not active in inhibiting [3H]dopamine uptake, indicating that the effect of meperidine was not via a classic μ-opioid receptor agonist action. Further, meperidine but not morphine displaced [3H]WIN 35,428 (2β-carbomethoxy-3β-(4-fluorophenyl)tropane) binding. These data suggest that the actions of meperidine that are atypical of opioids are due to activity at the dopamine transporter. In addition, meperidine appears to interact predominantly with the high-affinity component of the dopamine transporter, and this high-affinity component may be the site of importance for the production of cocaine's behavioral effects.

Original languageEnglish (US)
Pages (from-to)9-17
Number of pages9
JournalEuropean Journal of Pharmacology
Volume297
Issue number1-2
DOIs
StatePublished - Feb 15 1996
Externally publishedYes

Keywords

  • Cocaine
  • Dopamine transporter
  • Meperidine

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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