Serotonin-3 receptor and ethanol-stimulated dopamine release in the nucleus accumbens

Andrew D. Campbell, William J. McBride

Research output: Contribution to journalArticle

115 Scopus citations


The present study was undertaken to examine the involvement of activation of 5-HT3 receptors in the rat nucleus accumbens (Acb) on the effects of ethanol-induced increases of dopamine (DA) using the selective agonist 1-(m-chlorophenyl)-biguanide (CPBG). Perfusion of CPBG through the microdialysis probe concentration-dependently (3.3-100 μM) enhanced the extracellular levels of DA in the Acb. Extracellular DA concentrations increased as high as 1000% of baseline. The CPBG-induced increases in DA levels were Ca++ dependent and inhibited by local perfusion with the 5-HT3 antagonist ICS 205-930 (100 μM). In addition, CPBG at high concentrations caused significant decreases in the extracellular levels of DA metabolites. Intraperitoneal (IP) injection of 1 g/ kg ethanol produced no changes in extracellular DA levels in the Acb; coadministration of 1 g/kg ethanol (IP) and 5 μM CPBG (local) produced increases equal to 5 μM CPBG alone. Administration of 2 g/kg ethanol (IP) alone enhanced extracellular DA levels by ~60% above baseline, whereas local perfusion of 5 μM CPBG alone produced an increase of ~100% above baseline. The coadministration of 2 g/kg ethanol (IP) and 5 μM CPBG (local) enhanced DA levels by approximately 170% above baseline; this apparent additive enhancement was almost completely prevented when 100 μM ICS 205-930 was locally coperfused. Local administration of 3.3-100 μM CPBG did not alter the extracellular levels of serotonin or 5-hydroxyindoleacetic acid. The results support an involvement of 5-HT3 receptors in regulating DA release in the Acb, and also in mediating ethanol-induced DA release. However, the in vivo interaction of ethanol and 5-HT at the 5-HT3 receptor within the Acb is clearly not synergistic.

Original languageEnglish (US)
Pages (from-to)835-842
Number of pages8
JournalPharmacology, Biochemistry and Behavior
Issue number4
StatePublished - Aug 1995


  • 1-(m-chlorophenyl)-biguanide
  • 5-HT receptor
  • Dopamine
  • Ethanol
  • ICS 205-930
  • Microdialysis
  • Nucleus accumbens
  • Serotonin

ASJC Scopus subject areas

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

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