Atropine, an anticholinergic drug, impairs memory retrieval of a high consolidated avoidance response in mice

Immediate post-training intraperitoneal administration of the centrally acting anticholinesterase physostigmine (70.0, or 150.0 microg/kg) enhanced retention of male CF-1 mice tested 48 h after training in a one-trial step-through inhibitory avoidance task (0.8 mA, 50 Hz, 1 s footshock). The effect was observed in mice that received saline 30 min before the retention test; on the contrary, the pre-test administration of the centrally active muscarinic cholinergic antagonist, atropine (1.0 mg/kg, i.p.), but not methylatropine (1.0 mg/kg, i.p.), instead of saline, prevents the enhancement of retention induced by both doses of the anticholinesterase when given immediately after training. The high retention performance caused by post-training physostigmine was recovered following a second administration of the same doses of the drug, 10 min after the pre-test injections of atropine. Since, physostigmine do not influence memory retrieval when given prior to the retention test, and its post-training effects are not due to the induction of state-dependency, the recover of the high retention performance was probably due to a classical interaction between a muscarinic competitive antagonist and an indirect cholinergic agonist. Further, atropine probably does not modify the memory trace by erasing it, but by producing a poor retrieval.