Nefiracetam ameliorates associative learning impairment in the scopolamine-injected older rabbit.
Med Sci Monit
; 8(4): BR105-12, 2002 Apr.
Article
em En
| MEDLINE
| ID: mdl-11951055
ABSTRACT
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.CONCLUSIONS:
Nefiracetam had ameliorating effects on a task impaired in AD in an animal model of AD older rabbits with cholinergic system antagonism.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirrolidinonas
/
Aprendizagem por Associação
/
Envelhecimento
/
Nootrópicos
/
Condicionamento Palpebral
/
Deficiências da Aprendizagem
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Med Sci Monit
Assunto da revista:
MEDICINA
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos