LOW BUT NOT HIGH-DOSES OF BUSPIRONE REDUCE THE ANXIOGENIC EFFECTS OF DIAZEPAM WITHDRAWAL

After 21 days of treatment with diazepam (2 mg/kg/day IP) rats were tested 24 h after the last injection in the social interaction and elevated plus-maze tests of anxiety. Compared with control-treated rats, they showed significant decreases in social interaction, in the % numbers of entries onto open arms of the plus-maze and in the % of time spent on the open arms, indicating an anxiogenic response on withdrawal from diazepam. Buspirone (200-mu-g/kg SC) significantly increased social interaction in diazepam withdrawn rats and in the plus-maze also this dose significantly reversed the anxiogenic effects of diazepam withdrawal. Buspirone (400-mu-g/kg SC) was without effect in the plus-maze, but buspirone (800-mu-g/kg SC) significantly decreased the % of time spent on open arms in control-treated rats, indicating an anxiogenic effect. In the social interaction test buspirone (800-mu-g/kg SC) was without significant effect. The contrasting effects of the 200 and 800-mu-g/kg doses are discussed in terms of the pre- and post-synaptic actions of buspirone. The findings are consistent with earlier proposals that the increased anxiety during benzodiazepine withdrawal is at least partly caused by an increased release of hippocampal 5-HT.