Effects of sigma(1) receptor agonist SA4503 and neuroactive steroids on performance in a radial arm maze task in rats

This study examined the effects of sigma(1) receptor agonist SA4503 and neu roactive steroids dehydroepiandrosterone sulfate (DHEAS), pregnenolone sulf ate (PREGS) and progesterone (PROG) on spatial working and reference memory in a radial arm maze task in rats. The insertion of a 6-min delay between the 2nd and 3rd choices caused a specific decline in working memory, but ha d no effect on reference memory. This decline in working memory was improve d by SA4503, but not by DHEAS, PREGS or FROG. A non-competitive N-methyl-D- aspartate (NMDA) receptor antagonist dizocilpine significantly impaired bot h working and reference memory in the presence or absence of a delay. The d izocilpine-induced impairments in the presence of a 6-min delay were amelio rated by SA4503, DHEAS and PREGS, whereas FROG had no effect. The beneficia l effects of SA4503, DHEAS and PREGS were antagonized by treatment with sig ma(1) receptor antagonist N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)pheny l)-ethylamine hydrochloride (NE-100). Furthermore, FROG attenuated the amel iorating effects of SA4503, DHEAS and PREGS on dizocilpine-induced memory d eficits. These results suggest that sigma(1) receptors play a significant r ole in short-term working memory. Furthermore, it is suggested that DHEAS a nd PREGS ameliorate dizocilpine-induced memory impairments by acting as sig ma(1) receptor agonists, while FROG antagonizes their effects by acting as a sigma(1) receptor antagonist. (C) 2000 Elsevier Science Ltd. All rights r eserved.