The inhibitory avoidance test optimized for discovery of cognitive enhancers

Behav Res Methods. 2009 Aug;41(3):805-11. doi: 10.3758/BRM.41.3.805.

Abstract

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.

MeSH terms

  • Animals
  • Avoidance Learning / drug effects*
  • Donepezil
  • Drug Evaluation, Preclinical / instrumentation*
  • Drug Evaluation, Preclinical / methods*
  • Drug Interactions
  • Indans / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nootropic Agents / pharmacology
  • Piperidines / pharmacology
  • Scopolamine / pharmacology
  • Tacrine / pharmacology

Substances

  • Indans
  • Nootropic Agents
  • Piperidines
  • Tacrine
  • Donepezil
  • Scopolamine