MODIFICATION OF THE ANXIOLYTIC ACTION OF 5-MT1A COMPOUNDS BY GABA-BENZODIAZEPINE AGENTS IN RATS

The general purpose of the present study was to analyze the possible i nteractions between the GABA-benzodiazepine and the serotonin systems in the mediation of the antianxiety actions of 5-HT1A compounds. The a nxiolytic effect of buspirone (5 mg/kg), ipsapirone (5 mg/kg), indoren ate (5 mg/kg), and 8-OH-DPAT (0.5 mg/kg) was established in the rat bu rying behavior test. Flumazenil (5 mg/kg), but not bicuculline (2.5 mg /kg), effectively counteracted the reduction in burying behavior produ ced by buspirone, ipsapirone, and 8-OH-DPAT. These same 5-HT1A compoun ds, at subthreshold doses, produced an important reduction in burying behavior when combined with diazepam (0.25 mg/kg). The effect of indor enate was not altered by any of the antagonists and, when combined wit h diazepam it produced large increases in burying behavior latency. On ly buspirone alone and in combination with bicuculline or flumazenil i mpaired motor coordination as tested in the rota rod. Data are discuss ed on the bases of the interaction between the GABAergic and serotoner gic systems, stressing species differences and variations due to the a nimal model of anxiety. (C) 1998 Elsevier Science Inc.