Similar ameliorating effects of benzomorphans and 5-HT2 antagonists on drug-induced impairment of passive avoidance response in mice: comparison with acetylcholinesterase inhibitors.

Mice were trained to avoid electric shocks by means of step-down type passive avoidance learning tasks, and memory retention was measured 24 h after the training session. Memory impairment (amnesia) was produced by administering either p-chloroamphetamine (PCA), a serotonin (5-HT) releaser or scopolamine (SCOP), a muscarinic cholinoceptor antagonist, 30 min prior to the training session. Benzomorphans, 5-HT2 antagonists and acetylcholinesterase (AChE) inhibitors were administered immediately after the training session. PCA- but not SCOP-induced amnesia was attenuated by the post-training administration of two benzomorphans, (+)N-allylnormetazocine ((+)SKF-10,047) and (+/- )pentazocine ((+/- )PTZ). Similarly, PCA-induced amnesia was reversed by the post-training administration of 5-HT2 antagonists, ritanserin (RIT) and mianserin (MIA), but SCOP-induced amnesia was not. However, the AChE inhibitors, tetrahydroaminoacridine (THA) and physostigmine (PHY) attenuated both PCA- and SCOP-induced amnesia when administered immediately after the training session. These results indicated that benzomorphans and 5-HT2 antagonists have antiamnestic effects in mice, as do AChE inhibitors. In addition, it is interesting that the patterns of ameliorating effect of benzomorphans were similar to those of 5-HT2 antagonists, which differ from those of AChE inhibitors.