Opposing effects of ethanol and nicotine on hippocampal calbindin-D 28k expression

Patrick J. Mulholland, Barton R. Harris, Lincoln H. Wilkins, Rachel L. Self, John A. Blanchard, Robert C. Holley, John M. Littleton, Mark A. Prendergast

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Long-term ethanol exposure produces multiple neuroadaptations that likely contribute to dysregulation of Ca2+ balance and neurotoxicity during ethanol withdrawal. Conversely, nicotine exposure may reduce the neurotoxic consequences of Ca2+ dysregulation, putatively through up-regulation of the Ca2+-buffering protein calbindin-D28k. The current studies were designed to examine the extent to which 10-day ethanol exposure and withdrawal altered calbindin-D28k expression in rat hippocampus. Further, in these studies, we examined the ability of nicotine, through action at α7*-bearing nicotinic acetylcholine receptors (nAChRs), to antagonize the effects of ethanol exposure on calbindin-D 28k expression. Organotypic cultures of rat hippocampus were exposed to ethanol (50-100 mM) for 10 days. Additional cultures were exposed to 500 nM (-)-nicotine with or without the addition of 50 mM ethanol, 100 nM methyllycaconitine (an α7*-bearing nAChR antagonist), or both. Prolonged exposure to ethanol (≥50 mM) produced significant reductions of calbindin-D28k immunolabeling in all regions of the hippocampal formation, even at nontoxic concentrations of ethanol. Calbindin-D 28k expression levels returned to near-control levels after 72 h of withdrawal from 10-day ethanol exposure. Extended (-)-nicotine exposure produced significant elevations in calbindin-D28k expression levels that were prevented by methyllycaconitine co-exposure. Co-exposure of cultures to (-)-nicotine with ethanol resulted in an attenuation of ethanol-induced reductions in calbindin-D28k expression levels. These findings support the suggestion that long-term ethanol exposure reduces the neuronal capacity to buffer accumulated Ca2+ in a reversible manner, an effect that likely contributes to withdrawal-induced neurotoxicity. Further, long-term exposure to (-)-nicotine enhances calbindin-D28k expression in an α7* nAChR-dependent manner and antagonizes the effects of ethanol on calbindin-D28k expression.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
Issue number1-2
StatePublished - 2003

Bibliographical note

Funding Information:
This research was supported by grant AA00274 from the National Institute on Alcohol Abuse and Alcoholism (M.A.P.). We would like to thank D. Alex Gibson and Lauren B. Ho for their assistance with this study.


  • Alcoholism
  • Calbindin-D
  • Calcium
  • Neurotoxicity
  • Nicotine
  • Withdrawal

ASJC Scopus subject areas

  • Health(social science)
  • Biochemistry
  • Toxicology
  • Neurology
  • Behavioral Neuroscience


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