Nicotinic receptors in the dorsal and ventral hippocampus differentially modulate contextual fear conditioning

Hippocampus. 2012 Aug;22(8):1681-90. doi: 10.1002/hipo.22003. Epub 2012 Jan 23.


Nicotine administration alters various forms of hippocampus-dependent learning and memory. Increasing work has found that the dorsal and ventral hippocampus differentially contribute to multiple behaviors. Thus, the present study examined whether the effects of nicotine in the dorsal and ventral hippocampus have distinct influences on contextual fear learning in male C57BL/6J mice. Direct infusion of nicotine into the dorsal hippocampus resulted in an enhancement of contextual fear learning, whereas nicotine infused into the ventral hippocampus resulted in deficits. Nicotine infusions into the ventral hippocampus did not alter hippocampus-independent cued fear conditioning or time spent in the open arm of the elevated plus maze, a measure of anxiety, suggesting that the effects are due to alterations in contextual learning and not other general processes. Finally, results from using direct infusions of MLA, a low-affinity α7 nicotinic acetylcholine receptor (nAChR) antagonist, in conjunction with systemic nicotine, provide evidence that α7-nAChRs in the ventral hippocampus mediate the detrimental effect of ventral hippocampal nicotine on contextual fear learning. These results suggest that with systemic nicotine administration, competition exists between the dorsal and ventral hippocampus for behavioral control over contextual learning.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcholine / metabolism
  • Aconitine / administration & dosage
  • Aconitine / analogs & derivatives
  • Analysis of Variance
  • Animals
  • Conditioning, Psychological / drug effects*
  • Cues
  • Fear / drug effects*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Injections, Intraventricular
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Nicotine / administration & dosage*
  • Nicotinic Antagonists / administration & dosage
  • Receptors, Nicotinic / metabolism*
  • alpha7 Nicotinic Acetylcholine Receptor


  • Chrna7 protein, mouse
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • methyllycaconitine
  • Nicotine
  • Acetylcholine
  • Aconitine