Evidence for an anxiogenic action of AMPA receptor antagonists in the plus-maze test.

The effects of the non-NMDA receptor antagonists, the new alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-selective receptor antagonist, LY326325, and the AMPA/kainate-selective receptor antagonist, NBQX (6-nitro-7-sulfamoylbenzo(f)quinoxaline-2,3-(1H,4H)dione), on plus-maze behavior and locomotor activity were examined. LY326325 induced a dose-dependent decrease in the per cent time spent in open arms as well as in the per cent entries into the open arms. NBQX caused a dose-dependent reduction in the per cent time spent in open arms but had no effect on the per cent entries into the open arms. The behavioral actions of the AMPA receptor antagonists were observed at doses which had no influence on the locomotor activity of the animals. Based upon the current findings it is suggested that AMPA receptor antagonists produce a dose-dependent increase of anxiogenic behavior in the plus-maze test situation.