Aniracetam improves contextual fear conditioning and increases hippocampal gamma-PKC activation in DBA/2J mice

Hippocampus. 2002;12(1):76-85. doi: 10.1002/hipo.10008.


DBA/2J (D2) mice display poor contextual learning and have less membrane-bound hippocampal protein kinase C (PKC) compared with C57BL/6 (B6) mice. Aniracetam and oxiracetam were previously shown to improve contextual learning in D2 mice and increase PKC activity. This study investigated a possible mechanism for learning enhancement by examining the effects of aniracetam on contextual fear conditioning and activation of the y isoform of PKC (gamma-PKC) in male D2 mice. In comparison to animals treated with vehicle only (10% 2-hydroxypropyl-beta-cyclodextrin), mice treated with aniracetam (100 mg/kg) 30 min prior to fear conditioning training demonstrated significantly improved contextual learning when tested 30 min and 24 h after training. This corresponded with a significant increase in activated, membrane-bound hippocampal gamma-PKC 30 min after training. No increase in learning or gamma-PKC was found 5 min after training. These results suggest an altered time course of activation of gamma-PKC in response to treatment with aniracetam, which improves learning in D2 mice.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Conditioning, Psychological / drug effects*
  • Conditioning, Psychological / physiology*
  • Enzyme Activation / drug effects
  • Fear / drug effects
  • Fear / physiology*
  • Hippocampus / drug effects*
  • Hippocampus / enzymology*
  • Hippocampus / physiology
  • Isoenzymes / metabolism*
  • Learning / drug effects
  • Learning / physiology
  • Male
  • Memory / drug effects
  • Memory / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Nootropic Agents / pharmacology*
  • Protein Kinase C / metabolism*
  • Pyrrolidinones / pharmacology*
  • Species Specificity


  • Isoenzymes
  • Nootropic Agents
  • Pyrrolidinones
  • aniracetam
  • protein kinase C gamma
  • Protein Kinase C