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

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 γ isoform of PKC (γ‐PKC) in male D2 mice. In comparison to animals treated with vehicle only (10% 2‐hydroxypropyl‐β‐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 γ‐PKC 30 min after training. No increase in learning or γ‐PKC was found 5 min after training. These results suggest an altered time course of activation of γ‐PKC in response to treatment with aniracetam, which improves learning in D2 mice. Hippocampus 2002;12:76–85. © 2002 Wiley‐Liss, Inc.