Enhancement by secoverine and physostigmine of retention of passive avoidance response in mice.

A one-trial passive avoidance test in the mouse, in which drugs were injected intraperitoneally immediately after the shocked acquisition trial, was used. The effects of enhancing central cholinergic transmission on retention of passive avoidance was investigated using secoverine, which blocks muscarinic autoreceptor-mediated inhibition of acetylcholine release, and using physostigmine, an acetylcholinesterase inhibitor. Secoverine (1.0-5.0 mg/kg) and physostigmine (0.1-0.4 mg/kg) were found to improve retention of the avoidance response measured 24 h after acquisition. These effects were augmented when the two drugs were given in combination. In contrast, atropine (5.0 mg/kg) tended to impair retention of passive avoidance and blocked the facilitatory effects of physostigmine. The results support the hypothesis of a novel approach to treatment of memory disorders based on blockade of muscarinic autoreceptors, to augment central cholinergic activity.