Interactions between LY-354740, a Group II metabotropic agonist and the GABA(A)-benzodiazepine receptor complex in the rat elevated plus-maze

Flumazenil, a benzodiazepine (BZ) receptor antagonist, and naloxone, a non- selective mu -receptor antagonist, were used to investigate whether the anx iolytic action of LY354740 [1S,2S,5R,6S-2aminobicyclo[3.1.0]hexane-2,6-dica rboxyl monohydrate], a Group II metabotropic glutamate receptor agonist, wa s mediated through the benzodiazepine binding site on the GABAA receptor an d opioid pathways. LY354540 (1.0-10.0 mg/kg i.p.) induced dose-dependent an xiolytic-like effects in the rat elevated plus-maze. The anxiolytic-like ef fects of LY354740 (10.0 mg/kg) and the benzodiazepine receptor agonist, chl ordiazepoxide (CDP, 5.0 mg/kg i.p.) were blocked by flumazenil (15.0 mg/kg i.p.). By contrast, naloxone (10.0 mg/kg i.p.) failed to: affect the anxiol ytic-like effects of either LY354740 or CDP. The behaviour of animals treat ed with flumazenil or naloxone alone did not significantly differ from that of animals treated with vehicle alone. This study suggests that the anxiol ytic-like effects of LY354740 on the elevated plus-maze may be directly or indirectly mediated by the benzodiazepine binding site on the GABA(A) recep tor complex.