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Enhancement of hippocampally-mediated learning
and protein kinase C activity by oxiracetam in learning-impaired DBA/2
mice.
Fordyce DE, Clark
VJ, Paylor R, Wehner JM.
Institute for
Behavioural Genetics, University of Colorado at Boulder 80309-0447,
USA
The effects of oxiracetam on hippocampally-mediated learning
performance and hippocampal protein kinase C (PKC) were examined in
C57BL/6Ibg (C57) and DBA/2Ibg (DBA) mice. C57 and DBA mice were
subjected to daily injections of oxiracetam (50 mg/kg i.p.) or
vehicle (0.9% saline) for a total of 9 days. C57 and DBA mice were
examined on a modified version of the Morris water maze task and the
contextual fear conditioning task on the last 5 or 2 days,
respectively, of the 9-day treatment schedule. When compared with
controls, C57 and DBA oxiracetam-treated mice showed no difference
in motor skill capability to perform these complex learning tasks
(swim speed or ability to freeze). Hippocampal PKC activity was
measured in cytosolic, loosely-bound, and membrane-bound homogenate
fractions. Oxiracetam-treated DBA mice demonstrated a significant
increase in spatial learning performance as determined by the Morris
task. DBA performance was also improved in contextual learning as
determined by the fear conditioning task. The increase in spatial
learning performance was correlated to an increase in membrane-bound
PKC. No substantial improvements in C57 mice were observed on either
learning task nor did hippocampal PKC activity change in response to
oxiracetam treatment. These data demonstrate that the learning
impairment of DBA mice can be reversed by treatment with a nootropic
agent and support previous studies suggesting that PKC may be one
mechanism of action for oxiracetam.
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