Effects of amperozide in two animal models of anxiety.

The novel psychotropic agent amperozide (amp) was investigated in two different rat anxiety models, Vogel's conflict test (VT) and Montgomery's conflict test (MT). In the VT, amp in lower doses (0.2-0.6 mg/kg subcutaneously) increased the number of shocks accepted, as compared to controls. Pretreatment with the specific benzodiazepine receptor antagonist Ro 15-1788 (10.0 mg/kg orally) or the GABA-A receptor antagonist bicuculline (2.0 mg/kg intraperitoneally) antagonized the anticonflict effect of amp (0.4 mg/kg subcutaneously). At the highest dose tried (2.0 mg/kg subcutaneously) amp instead decreased the number of shocks accepted. Both 0.4 mg/kg and 2.0 mg/kg of amp raised the shock threshold, as compared to controls. The latter dose also decreased the motivation to drink. Pretreatment with Ro 15-1788 (10.0 mg/kg orally) did not significantly change the shock threshold or the drinking motivation, as compared to the group receiving amp alone. In the MT, amp (0.05-0.1 mg/kg subcutaneously) increased the percentage time spent in the open arms, while no changes were seen in the number of entries made into these arms. After higher doses (0.4-0.8 mg/kg subcutaneously) no differences, as compared to controls, were observed. Amp (1 nM-10microM) exhibited no affinity for 3H-flunitrazepam binding sites in mouse forebrain membranes in vitro. Taken together, the present data suggest that amp in low doses produces anticonflict (anxiolytic-like) effects. These effects appear to be mediated through an indirect (via 5-HT and/or DA systems?) activation of the GABA/benzodiazepine chloride ionophore receptor complex.