Article

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

Eli Lilly and Co., Lilly Research Laboratories, Indianapolis, IN 46285-0510, USA.
Neuropharmacology (impact factor: 4.81). 07/2001; 40(8):1028-33. DOI:10.1016/S0028-3908(00)00194-5 pp.1028-33
Source: PubMed

ABSTRACT LY392098 is a member of a novel class of biarylpropylsulfonamides that potentiates 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 identify clinically useful antidepressants. LY392098 reduced immobility in the forced swim test in both rats and mice, with a minimum effective dose of 0.5 mg/kg (i.p.) in both species. LY392098 (0.1-10 mg/kg, i.p.) did not affect motor activity of rats, indicating that the ability of this compound to reduce immobility in the forced swim test is unrelated to a motor stimulant action. 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-competitive AMPA antagonist (LY300168) blocked the activity of LY392098 in the forced swim test, but did not affect imipramine-induced reductions in immobility. Thus, AMPA receptor activation appears to be required for the antidepressant-like effect of LY392098, but not imipramine. These findings indicate that biarylpropylsulfonamides, exemplified by LY392098, may represent a novel class of antidepressants.

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Keywords

AMPA receptor activation
 
antidepressant-like effect
 
antidepressants
 
behavioral despair
 
clinically useful antidepressants
 
exemplified
 
imipramine
 
imipramine-induced reductions
 
immobility
 
mice
 
minimum effective dose
 
motor activity
 
motor stimulant action
 
non-competitive AMPA antagonist
 
novel class
 
potentiates AMPA receptor-mediated responses
 
tail suspension test
 
tail suspension tests