The Hippocampus and Cingulate Cortex Differentially Mediate the Effects of Nicotine on Learning Versus on Ethanol-Induced Learning Deficits Through Different Effects at Nicotinic Receptors

Danielle Gulick, Thomas J. Gould

Research output: Contribution to journalArticle

21 Scopus citations


The current study examined the effects of nicotine infusion into the dorsal hippocampus or anterior cingulate on fear conditioning and on ethanol-induced deficits in fear conditioning, and whether these effects involved receptor activation or inactivation. Conditioning consisted of two white noise (30 s, 85 dB)-foot-shock (2 s, 0.57 mA) pairings. Saline or ethanol was administered to C57BL/6 mice 15 min before training and saline or nicotine was administered 5 min before training or before training and testing. The ability of the high-affinity nicotinic acetylcholinergic receptor (nAChR) antagonist dihydro-Β-erythroidine (DHΒE) to modulate the effects of ethanol and nicotine was also tested; saline or DHΒE was administered 25 (injection) or 15 (infusion) minutes before training or before training and testing. Infusion of nicotine into the hippocampus enhanced contextual fear conditioning but had no effect on ethanol-induced learning deficits. Infusion of nicotine into the anterior cingulate ameliorated ethanol-induced deficits in contextual and cued fear conditioning but had no effect on learning in ethanol-naive mice. DHΒE blocked the effects of nicotine on ethanol-induced deficits; interestingly, DHΒE alone and co-administration of subthreshold doses of DHΒE and nicotine also ameliorated ethanol-induced deficits but failed to enhance learning. Finally, DHΒE failed to ameliorate ethanol-induced deficits in Β2 nAChR subunit knockout mice. These results suggest that nicotine acts in the hippocampus to enhance contextual learning, but acts in the cingulate to ameliorate ethanol-induced learning deficits through inactivation of high-affinity Β2 subunit-containing nAChRs.

Original languageEnglish (US)
Pages (from-to)2167-2179
Number of pages13
Issue number9
Publication statusPublished - Aug 1 2009


All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

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