Post-training injection of the acetylcholine M2 receptor antagonist AF-DX 116 improves memory

Brain Res. 1990 Jul 30;524(1):72-6. doi: 10.1016/0006-8993(90)90493-u.

Abstract

The present study examined the effect of systemic post-training administration of the acetylcholine muscarinic M2 receptor antagonist AF-DX 116 on the acquisition of two 8-arm radial maze tasks. On a win-stay visual discrimination task, a light cue signalled the location of food in 4 randomly selected maze arms, and rats were required to visit each of the 4 lit arms twice within a trial. Rats were given one trial per day and injected immediately post-training on day 5. AF-DX 116 (0.5 and 1.0 mg/kg) significantly improved win-stay acquisition relative to vehicle-injected controls. On a win-shift task, rats were allowed to visit 4 randomly selected maze arms, followed by a delay period. After the delay, rats were returned to the maze for a retention test in which only those 4 arms not visited prior to the delay contained food. On the test (i.e. drug) trial, rats were removed from the maze after the first 4 choices and injected with AF-DX 116 or vehicle. The retention test was given following an 18 h delay. AF-DX 116 (2.0 mg/kg) significantly improved retention relative to vehicle controls. When the injections were given 2 h post-training, no effect on retention was observed in either task. The results demonstrate that post-training injection of the selective M2 receptor antagonist AF-DX 116 improves memory in a time-dependent manner. The findings may have implications for the cholinergic pharmacotherapy of Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Learning
  • Male
  • Memory / drug effects*
  • Parasympatholytics / pharmacology*
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / pharmacology
  • Rats
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / physiology*
  • Reference Values
  • Time Factors

Substances

  • Parasympatholytics
  • Receptors, Muscarinic
  • Pirenzepine
  • otenzepad