Reduction of 4-cyclohexyl-1-[(1R)-1,2-diphenylethyl]-piperazine-induced memory impairment of passive avoidance performance by sigma 1 receptor agonists in mice.
Intraperitoneal administration of 4-cyclohexyl-1-[(1R)-1,2-diphenylethyl]-piperazine (CDEP) immediately after the training session produced significant memory impairment in the mouse passive avoidance performance. Interestingly, this memory impairment was alleviated by subcutaneous administrations of sigma receptor agonists, (+)-N-allylnormetazocine ((+)-SKF-10,047), (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP) and 1,3-di(2-tolyl)guanidine (DTG) immediately after the training session. In particular, the remarked recovery for this memory impairment was produced by (+)-SKF-10,047. A receptor binding study showed that CDEP possessed high affinities for both sigma 1 and sigma 2 receptor subtypes (IC50 1.4 +/- 0.3 nM for sigma 1 receptor subtype, 1.8 +/- 0.3 nM for sigma 2 receptor subtype), while (+)-SKF-10,047 had a high selectivity for the sigma 1 receptor subtype. These findings suggest that the sigma receptor, particularly sigma 1 receptor subtype, may play an important role in the CDEP-induced impairment of learning and memory processes.
Matsuno
K
K
Central Research Laboratory, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Senda
T
T
Kobayashi
T
T
Murai
M
M
Mita
S
S
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects*; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology; D051379:Mice; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010879:Piperazines / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010880:Piperidines / Q000494:pharmacology; D011869:Radioligand Assay; D017480:Receptors, sigma / Q000187:drug effects*
C117547:4-cyclohexyl-1-(1,2-diphenylethyl)piperazine; D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D010879:Piperazines; D010880:Piperidines; D017480:Receptors, sigma; C012134:SK&F 10047; C026539:preclamol; D010620:Phenazocine