Scimago Lab
powered by Scopus
call: +1.631.470.9640
Mon-Fri 10 am - 2 pm EST


Medical Science Monitor Basic Research


eISSN: 1643-3750

Get your full text copy in PDF

Nefiracetam ameliorates associative learning impairment in the scopolamine-injectedolder rabbit.

John Green, Boris Heifets, Jonathan Pak, Michelle Pak, Diana Woodruff-Pak

Med Sci Monit 2002; 8(4): BR105-112

ID: 420883

BACKGROUND: The cognition-enhancing drug, nefiracetam, is in Phase IIIclinical trials to treat memory impairment in Alzheimer's disease (AD). Nefiracetam ameliorates acquisitionof delay eyeblink classical conditioning in older rabbits, a form of associative learning with strikingbehavioral and neurobiological similarities in rabbits and humans. In both species, delay eyeblink conditioningengages the septo-hippocampal cholinergic system and is disrupted when the cholinergic system is antagonized.Delay eyeblink classical conditioning is impaired in normal aging and severely disrupted in AD. MATERIAL/METHODS:To test further the efficacy of nefiracetam in an animal model that mimics some of the neurobiologicaland behavioral effects present in AD, we tested 56 older rabbits assigned to 7 treatment groups in the750 ms delay eyeblink conditioning procedure. Older rabbits were injected with 1.5 mg/kg scopolamineto simulate disruption of the cholinergic system in AD. Three doses of nefiracetam (5, 10, or 15 mg/kg)were also injected in older rabbits receiving 1.5 mg/kg scopolamine. Control groups were treated with1.5 mg/kg scopolamine + vehicle, vehicle alone, or explicitly unpaired presentations of conditioningstimuli and vehicle or 1.5 mg/kg scopolamine + 15 mg/kg nefiracetam. RESULTS: Rabbits injected with 1.5mg/kg scopolamine alone were impaired, but a dose of 15 mg/kg nefiracetam reversed significantly thebehavioral impairment. CONCLUSIONS: Nefiracetam had ameliorating effects on a task impaired in AD inan animal model of AD: older rabbits with cholinergic system antagonism.

This paper has been published under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.
I agree