Development of rapid tolerance to ethanol-stimulated serotonin release in the ventral hippocampus

Dan J. Bare, Jamie H. McKinzie, William J. McBride

Research output: Contribution to journalArticle

25 Scopus citations


This study was designed to examine the effects of acute intraperitoneal (ip) ethanol injection on the extracellular levels of serotonin (5HT) in the ventral hippocampus (vHIP) and to determine whether a single prior exposure to ethanol could alter the response to a second dose of ethanol given 24 hr later. In the first experiment, in vivo microdialysis coupled with high pressure liquid chromatography-electrochemical detection (HPLC-EC) was used to assess the effects of 1.0, 1.75, and 2.5 g/kg ethanol on vHIP 5-HT extracellular levels in ethanol-naive adult male Wistar rats. The largest dose significantly increased the extracellular concentration of 5-HT (p < 0.001) to a maximum of approximately 180% of baseline values within 50 min; thereafter, the levels of 5-HT began to return toward baseline. The 1.75 g/kg dose also transiently increased 5-HT levels above baseline; however, no significant increase was observed with 1.0 g/kg ethanol. The results of the second experiment demonstrated that the ip dose of 2.5 g/kg ethanol had no significant effect on the extracellular levels of 5-HT if rats had been given a single ip 2.5 g/kg dose of ethanol 24 hr earlier. Because the vHIP receives a major 5-HT input from the median raphe nucleus (MRN), the results suggest that acute ethanol activates the MRN 5-HT system projecting to the vHIP and that rapid tolerance develops to the activating effects of alcohol on this pathway.

Original languageEnglish (US)
Pages (from-to)1272-1276
Number of pages5
JournalAlcoholism: Clinical and Experimental Research
Issue number6
StatePublished - Sep 1998


  • Median Raphe Nucleus
  • Microdialysis
  • Rapid Alcohol Tolerance
  • Serotonin Release
  • Ventral Hippocampus

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

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