Antidepressant-like actions of an AMPA receptor potentiator (LY392098)

LY392098 is a member of a novel class of biarylpropylsulfonamides that pote ntiates AMPA receptor-mediated responses both in vitro and in vivo. In this study, the effects of LY392098 were evaluated in two "behavioral despair" models (the forced swim and tail suspension tests) commonly used to identif y clinically useful antidepressants. LY392098 reduced immobility in the for ced swim test in both rats and mice, with a minimum effective dose of 0.5 m g/kg (i.p.) in both species. LY392098 (0.1-10 mg/kg, i.p.) did not affect m otor activity of rats. indicating that the ability of this compound to redu ce immobility in the forced swim test is unrelated to a motor stimulant act ion. LY392098 also reduced immobility in the tail suspension test in a dose -dependent manner, with a minimum effective dose of 5 mg/kg (i.p). A non-co mpetitive AMPA antagonist (LY300168) blocked the activity of LY392098 in th e forced swim test. but did not affect imipramine-induced reductions in imm obility. Thus, AMPA receptor activation appears to be required for the anti depressant-like effect of LY392098. but not imipramine. These findings indi cate that biarylpropylsulfonamides, exemplified by LY392098. may represent a novel class of antidepressants. (C) 2001 Elsevier Science Ltd. All rights reserved.