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.
Matsuno
K
K
Central Research Laboratories, Santen Pharmaceutical Co., Osaka, Japan.
Senda
T
T
Matsunaga
K
K
Mita
S
S
Kaneto
H
H
D000109:Acetylcholine / Q000378:metabolism; D000647:Amnesia / Q000139:chemically induced / Q000517:prevention & control; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001575:Benzomorphans / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004597:Electroshock; D008297:Male; D051379:Mice; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D010133:p-Chloroamphetamine / Q000494:pharmacology
D001575:Benzomorphans; D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D012702:Serotonin Antagonists; D010133:p-Chloroamphetamine; D000109:Acetylcholine