Quantitative effects of nefiracetam on spatial learning of rats after cerebral embolism.
Recent studies have shown that nefiracetam ameliorates cognitive dysfunction because of ischemia when behavioral testing occurs during treatment. We sought to determine if there was a persistent effect after treatment, by testing spatial learning of embolized rats after nefiracetam therapy.


METHODS
Male Sprague Dawley rats (250 to 300 g) were divided into 3 categories. The control group (n = 5) underwent no surgery or cerebral embolism. The vehicle group (n = 12) was anesthetized with halothane, underwent surgery, injected with intracarotid microspheres, and given orally 5 mL/kg of the vehicle (0.5% aqueous sodium carboxymethyl cellulose) for 21 days. The nefiracetam group (n = 12) was embolized and treated orally with 30 mg/kg nefiracetam (6 mg/mL in vehicle) for 21 days. Outcome was determined with visual spatial learning after the end of treatment.


RESULTS
Embolization caused a significant impairment in visual spatial learning, which nefiracetam completely ameliorated (group main effect, F(2,444) = 6.4, P = .002). Mean latency to the escape was 35 +/- 6 seconds for the vehicle group versus 18 +/- 4 seconds for the nefiracetam group, after 4 days of testing. This effect persisted after a further interval of 10 days (retention test). A reversal test (to assess working memory for new information) yielded mean latencies of 26 +/- 6 seconds for the control group, 49 +/- 5 seconds for vehicle, and 25 +/- 4 seconds for nefiracetam (group main effect, F(2,109) = 8.0, P = .0005, Newman-Keuls, P < .05), showing that both the control and nefiracetam groups were different from the vehicle group.


CONCLUSIONS
Nefiracetam therapy improves the learning behavior of embolized rats. The results are not caused by an activating effect of the drug because the animals are tested after the treatment period is over and because the beneficial effect is seen using the delayed retention test. Finally, working memory is markedly preserved by nefiracetam, an effect observed several weeks after treatment.
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Department of Neurosciences, UCSD School of Medicine, and Neurology, Veterans Administration Medical Center, San Diego, CA, USA.
Shin
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Jackson-Friedman
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Lyden
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