Nefiracetam ameliorates associative learning impairment in the scopolamine-injected older rabbit

Jonathan T. Pak, John T. Green, Boris Heifets, Michelle H. Pak, Diana S. Woodruff-Pak

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background: The cognition-enhancing drug, nefiracetam, is in Phase III clinical trials to treat memory impairment in Alzheimer's disease (AD). Nefiracetam ameliorates acquisition of delay eyeblink classical conditioning in older rabbits, a form of associative learning with striking behavioral and neurobiological similarities in rabbits and humans. In both species, delay eyeblink conditioning engages 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 neurobiological and behavioral effects present in AD, we tested 56 older rabbits assigned to 7 treatment groups in the 750 ms delay eyeblink conditioning procedure. Older rabbits were injected with 1.5 mg/kg scopolamine to 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 with 1.5 mg/kg scopolamine + vehicle, vehicle alone, or explicitly unpaired presentations of conditioning stimuli and vehicle or 1.5 mg/kg scopolamine + 15 mg/kg nefiracetam. Results: Rabbits injected with 1.5 mg/kg scopolamine alone were impaired, but a dose of 15 mg/kg nefiracetam reversed significantly the behavioral impairment. Conclusion: Nefiracetam had ameliorating effects on a task impaired in AD in an animal model of AD: older rabbits with cholinergic system antagonism.

Original languageEnglish (US)
Pages (from-to)BR105-BR112
JournalMedical Science Monitor
Issue number4
StatePublished - 2002
Externally publishedYes


  • Acetylcholine
  • Alzheimer's disease
  • Cognition-enhancing
  • Eyeblink classical conditioning
  • Muscarinic acetylcholine receptors

ASJC Scopus subject areas

  • Medicine(all)


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