Anxiolytic-like effect of ( S)-WAY 100135, a 5-HT 1A receptor antagonist, in the murine elevated plus-maze test

Abstract

The effects of ( S)-WAY 100135 (( S)- N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenyl-propanamide dihydrochloride; 2.5–20.0 mg/kg), a 5-HT 1A receptor antagonist, on the behaviour of male mice were examined in the elevated plus-maze test of anxiety. An ethological scoring technique was used to provide a comprehensive profile of drug action. Only minor changes in behaviour were observed at 2.5 and 5.0 mg/kg, and consisted of reductions in some (though not all) risk assessment measures. At 10 mg/kg, the compound increased percent open arm entries and percent open arm time, without altering general activity levels. This classic anxiolytic-like profile was confirmed by major reductions in risk assessment measures including protected head-dips and protected streched attend postures. Although many of the same changes were also observed at 20 mg/kg, the absence of an effect on percent open arm time and a tendency towards increased non-exploratory behaviour suggested (1) some loss of anxiolytic activity and (2) a possible contribution of non-specific factors at higher doses. Present findings indicate that ( S)-WAY 100135 produces clear anxiolytic-like effects in the murine elevated plus-maze, a profile that can be distinguished from that produced by 5-HT 1A receptor partial agonists in the same test.