REDUCTION OF EXYL-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-diphenylethy l]-piperazine (CDEP) immediately after the training session produced s ignificant memory impairment in the mouse passive avoidance performanc e. 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 trainin g session. In particular, the remarked recovery for this memory impair ment was produced by (+)-SKF-10,047. A receptor binding study showed t hat CDEP possessed high affinities for both sigma(1) and sigma(2) rece ptor 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 sug gest that the sigma receptor; particularly sigma(1) receptor subtype, may play an important role in the CDEP-induced impairment of learning and memory processes. (C) 1998 Prous Science. All rights reserved.