Facilitation of memory storage by the acetylcholine M2 muscarinic receptor antagonist AF-DX 116.
Post-training administration of the acetylcholine muscarinic M2 presynaptic receptor antagonist AF-DX 116 (0.1-10.0 mg/kg, ip), facilitated 48 h retention, in male Swiss mice, of a one-trial step-through inhibitory avoidance task. The dose-response curve was an inverted U. AF-DX 116 did not increase the retention latencies of mice that had not received a footshock during training. The influence of AF-DX 116 (1 mg/kg, ip) on retention was time-dependent, which suggests that the drug facilitated memory storage. The memory facilitation induced by AF-DX 116 (1 mg/kg, ip) was prevented by atropine (0.5 mg/kg, ip) administered after training, but 10 min prior to AF-DX 116 treatment. In contrast, neither methylatropine (0.5 mg/kg, ip), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, ip) or hexamethonium (5 mg/kg, ip), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training AF-DX 116 on retention. Low subeffective doses of the central acting anticholinesterase physostigmine (35 micrograms/kg, ip), administered immediately after training, and AF-DX 116 (0.1 mg/kg, ip), given 10 min after training, acted synergistically to improve retention. The effects of AF-DX 116 (0.1 mg/kg, ip) were not influenced by the peripherally acting anticholinesterase neostigmine (35 micrograms/kg, ip). Considered together, these findings suggest that the activation of a muscarinic cholinergic presynaptic inhibitory mechanism, probably by increasing brain acetylcholine release, may modulate the activity of post-training processes involved in memory storage.
Baratti
C M
CM
Laboratorio de Neurofarmacología de Procesos de Memoria, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Opezzo
J W
JW
Kopf
S R
SR
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D004357:Drug Synergism; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D009388:Neostigmine / Q000494:pharmacology*; D010276:Parasympatholytics / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology*; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects*
D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D009388:Neostigmine; D010890:Pirenzepine; D001285:Atropine; D010830:Physostigmine; C048593:otenzepad