Sustained inhibition of brotizolam induced anterograde amnesia by norharmane and retrograde amnesia by L-glutamic acid in mice

Behav Brain Res. 2007 Aug 22;182(1):12-20. doi: 10.1016/j.bbr.2007.04.022. Epub 2007 May 3.

Abstract

Benzodiazepines such as diazepam, lorazepam, are reported to produce anterograde amnesia but these do not affect the retrieval mechanism. Triazodiazepines such as alprazolam, triazolam and brotizolam produce both anterograde and retrograde amnesia. Because benzodiazepine receptor antagonists are known to reverse anterograde amnesia, we wanted to test if inverse agonist can also improve learning and memory. The present study was designed to investigate the effect of norharmane (benzodiazepine receptor inverse agonist) and L-glutamic acid (glutamate receptor agonist) on brotizolam induced anterograde and retrograde amnesia using Morris water maze task in mice. Norharmane reversed anterograde amnesia induced by brotizolam and did not reverse retrograde amnesia induced by it. L-Glutamic acid attenuated retrograde amnesia but did not affect anterograde amnesia induced by brotizolam. These results provide an opportunity to understand the mechanisms of anterograde and retrograde amnesia which may occur with interaction of presynaptic molecules or LTP modulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amnesia, Anterograde / chemically induced
  • Amnesia, Anterograde / drug therapy*
  • Amnesia, Retrograde / chemically induced
  • Amnesia, Retrograde / drug therapy*
  • Analysis of Variance
  • Animals
  • Avoidance Learning / drug effects
  • Azepines / therapeutic use*
  • Behavior, Animal / drug effects
  • Carbolines
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • Glutamic Acid
  • Harmine / analogs & derivatives
  • Hypnotics and Sedatives / therapeutic use*
  • Male
  • Maze Learning / drug effects
  • Mice
  • Reaction Time / drug effects
  • Reaction Time / physiology

Substances

  • Azepines
  • Carbolines
  • Hypnotics and Sedatives
  • Glutamic Acid
  • Harmine
  • brotizolam
  • norharman