The putative AMPA receptor antagonist, LY326325, produces anxiolytic-like effects without altering locomotor activity in rats.

Anxiolytic-like effects produced by the novel, water-soluble AMPA/kainate receptor antagonist, LY326325 (3RS,4aRS,6RS,8aRS)-6-[2-(1(2)H-tetrazole-5-yl)e thyl]decahydro-isoquinoline-3-carboxylic acid), were examined in the elevated plus-maze and in a conflict-suppressed drinking situation. Administration of low doses (0.5, 1.2, and 5 mg/kg; i.p., -30 min) of LY326325 to Sprague-Dawley rats did not alter the percentage of entries into the open arms of the plus-maze, whereas only one dose of LY326325 (1 mg/kg) produced a slight, but significant, increase of the time spent in the open arms of the plus maze. In the conflict-suppressed drinking test, similar doses of LY326325 (2.5 and 5 mg/kg; i.p., -30 min) caused a dose-dependent and significant increase of punished drinking behavior without having any significant effects on unpunished drinking. The anxiolytic-like effects of LY326325 in the plus-maze and in the anticonflict tests were observed at doses, which, by themselves, had no influence on various measures of locomotor activity, i.e., horizontal activity, forward locomotion, and corner time. Our data suggest that the putative AMPA/glutamate receptor antagonist, LY326325, produces anxiolytic-like effects similar to those of diazepam in the conflict-suppressed drinking test, but displays considerably weaker anxiety-reducing properties compared to diazepam in the elevated plus-maze.