Chronic, but not acute, nicotine exposure attenuates ethanol withdrawal-induced hippocampal damage in vitro

Mark A. Prendergast, Barton R. Harris, Sveta Mayer, John M. Littleton

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


Background: Long-term ethanol use and long-term tobacco use frequently occur together, which suggests concurrent dependence on ethanol and nicotine. Consequences of this form of polydrug dependence are not well understood, however. Previous evidence suggests detrimental effects of long-term ethanol and beneficial effects of nicotine exposure on neuronal viability. Thus, the present study was designed to use an organotypic hippocampal slice culture model to examine the ability of chronic and acute nicotine exposure to reduce neurotoxicity associated with withdrawal from long-term ethanol exposure. Methods and Results: Twenty-four hours of withdrawal after continuous 10 day ethanol exposure (50 or 100 mM in culture medium) resulted in cytotoxicity in hippocampal slice explants obtained from neonatal rat, most notably in pyramidal cell layers of the CA1 region. Exposure of slices to the N-methyl-D-aspartate receptor blocker MK-801 during ethanol withdrawal significantly reduced this toxicity. Exposure of slices to nicotine (0.1-10.0 μM) during the 24 hr withdrawal period did not reduce hippocampal damage. However, treatment of slices with nicotine (0.1-10.0 μM) during 10 days of ethanol exposure was associated with significant reductions in subsequent withdrawal-induced cytotoxicity, an effect reduced by mecamylamine coexposure with nicotine and ethanol. Conclusions: These findings indicate the development of marked hippocampal neurotoxicity during withdrawal from long-term ethanol exposure that is mediated, in part, by overactivation of N-methyl-D-aspartate receptors. Furthermore, these data suggest that one consequence of concurrent dependence on ethanol and nicotine may be reduced neurological damage associated with ethanol withdrawal.

Original languageEnglish
Pages (from-to)1583-1592
Number of pages10
JournalAlcoholism: Clinical and Experimental Research
Issue number10
StatePublished - 2000


  • Ethanol withdrawal
  • Excitotoxicity
  • Neurotoxicity
  • Nicotine

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health


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