Post-training injection of the acetylcholine M2 receptor antagonist AF-DX 116 improves memory.
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.
Packard
M G
MG
Department of Psychology, McGill University, Montreal, Que., Canada.
Regenold
W
W
Quirion
R
R
White
N M
NM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007858:Learning; D008297:Male; D008568:Memory / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology*; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D013997:Time Factors
D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D010890:Pirenzepine; C048593:otenzepad