The 5-HT3 antagonist zacopride attenuates cocaine-induced increases in extracellular dopamine in rat nucleus accumbens

Charles S. McNeish, Adena L. Svingos, Robert Hitzemann, Robert E. Strecker

Research output: Contribution to journalArticle

49 Scopus citations


Pretreatment with the serotonin-3 (5-HT3) antagonist racemic (±)-Zacopride hydrochloride (ZAC, 0.1 mg/kg, IP) has been previously found to completely abolish the locomotor activity induced by cocaine (10 mg/kg, IP). To determine if this effect was mediated by fluctuations in the extracellular levels of forebrain dopamine (DA), we examined the ability of ZAC to attenuate cocaine-induced increases in extracellular DA levels. Microdialysis samples were collected from the nucleus accumbens region (NAS) of awake, male, Sprague-Dawley rats. ZAC treatment alone (0.1 mg/kg, IP) did not alter DA levels relative to baseline. However, this dose of ZAC given 1 h prior to cocaine challenge (10 mg/kg, IP) caused a 27% reduction in the peak level of extracellular DA produced by cocaine, relative to saline-pretreated control animals. These results suggest that the ability of ZAC to attenuate cocaine-induced increases in extracellular DA levels may contribute to ZAC's ability to suppress cocaine-induced locomotor activity in the rat. However, additional neurochemical mechanisms are likely to be important in mediating the robust behavioral effects previously reported.

Original languageEnglish (US)
Pages (from-to)759-763
Number of pages5
JournalPharmacology, Biochemistry and Behavior
Issue number4
StatePublished - Aug 1993



  • Cocaine
  • Dopamine release
  • Microdialysis
  • Nucleus accumbens
  • Rat
  • Serotonin-3 receptor
  • Zacopride

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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