The inhibitory avoidance test optimized for discovery of cognitive enhancers.
In the present article, we describe a new protocol for the inhibitory avoidance test, with a dual purpose: (1) to provide a less variable and more reliable assessment of the efficacy of potential cognitive enhancers in antagonizing scopolamine-induced long-term-memory deficits, and (2) to secure a high throughput for pharmacological screening of cognitive enhancers. The new protocol consists of two acquisition trials that are followed 24 h later by a single retention trial. In the present study, this protocol clearly dissociated the frequency distributions of retention latencies between scopolamine- and vehicle-treated groups and allowed validation by means of two acetylcholinesterase inhibitors-tacrine and donepezil-that proved to be active in counteracting the scopolamine-induced memory deficit. This protocol also produced stability of the behavioral response to pharmacological agents over a 3-year period. A statistical power analysis indicated that, depending on the efficacy of the drug/dose, a sample size of 5-12 mice was required in order to show a reversal of the scopolamine-induced memory deficit. The double-trial acquisition protocol is suitable for testing cognitive enhancers, while also providing a clearly enhanced throughput.
Detrait
Eric R A Y
ER
CNS Pharmacology Department-Cognitive Psychopharmacology, UCB Pharma, Braine-l'Alleud, Belgium. eric.detrait@ucb-group.com
Hanon
Etienne
E
Dardenne
Bertrand
B
Lamberty
Yves
Y
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D000077265:Donepezil; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000379:methods*; D004347:Drug Interactions; D007189:Indans / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018697:Nootropic Agents / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology; D013619:Tacrine / Q000494:pharmacology
D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D013619:Tacrine; D000077265:Donepezil; D012601:Scopolamine