Chronic nicotine exposure inhibits estrogen-mediated synaptic functions in hippocampus of female rats

Ami P. Raval, Justin T. Sick, Gabriel J. Gonzalez, R. Anthony DeFazio, Chuanhui Dong, Thomas J. Sick

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Nicotine, the addictive agent in cigarettes, reduces circulating estradiol-17β (E 2) and inhibits E 2-mediated intracellular signaling in hippocampus of female rats. In hippocampus, E 2-signaling regulates synaptic plasticity by phosphorylation of the N-methyl-d-aspartic acid receptor subunit NR2B and cyclic-AMP response element binding protein (pCREB). Therefore, we hypothesized that chronic nicotine exposure induces synaptic dysfunction in hippocampus of female rats. Female rats were exposed to nicotine or saline for 16days followed by electrophysiological analysis of hippocampus. Briefly, population measurements of excitatory post-synaptic field potentials (fEPSPs) were recorded from stratum radiatum of the CA1 hippocampal slice subfield. A strict software-controlled protocol was used which recorded 30min of baseline data (stimulation rate of 1/min), a paired-pulse stimulation sequence followed by tetanic stimulation, and 1h of post-tetanus recording. EPSP amplitude and the initial EPSP slope were measured off-line. We then investigated by Western blot analysis the effects of nicotine on hippocampal estrogen receptor-beta (ER-β), NR2B and pCREB. The results demonstrated significantly decreased post-tetanic potentiation and paired-pulse facilitation at the 40, and 80ms interval in nicotine-exposed rats compared to the saline group. Western blot analysis revealed that nicotine decreased protein levels of ER-β, NR2B, and pCREB. We also confirmed the role of E 2 in regulating NR2B and pCREB phosphorylation by performing Western blots in hippocapmal tissue obtained from E 2-treated ovariectomized rats. In conclusion, chronic nicotine exposure attenuates short-term synaptic plasticity, and the observed synaptic defects might be a consequence of loss of estradiol-17β-signaling. However, determining the exact molecular mechanisms of chronic nicotine exposure on synaptic plasticity specific to the female brain require further investigation.

Original languageEnglish (US)
Pages (from-to)41-46
Number of pages6
JournalNeuroscience Letters
Issue number1
StatePublished - May 23 2012


  • Cyclic-AMP response element binding
  • Estrogen receptors
  • Hippocampus
  • Long-term potentiation
  • Paired-pulse modulation

ASJC Scopus subject areas

  • Neuroscience(all)


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