Aniracetam improves contextual fear conditioning and increases hippocampal gamma-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 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.
Smith
Amy M
AM
Institute for Behavioral Genetics and Department of Psychology, University of Colorado, Boulder 80309, USA.
Wehner
Jeanne M
JM
D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism*; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018697:Nootropic Agents / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology*; D013045:Species Specificity
D007527:Isoenzymes; D018697:Nootropic Agents; D011760:Pyrrolidinones; C036466:aniracetam; C087857:protein kinase C gamma; D011493:Protein Kinase C