The effect of glucocorticoids on the anxiolytic efficacy of buspirone

Rationale: The serotonergic system and the hypothalamus-hypophysis-adrenoco rtical axis reciprocally influence each other. Therefore, the interaction b etween stress and serotonergic anxiolytics should be of major concern for b oth laboratory investigations and clinical treatment. Objectives: We have s tudied the effects of the serotonergic anxiolytic buspirone in rats in whic h basal levels of glucocorticoids were low and stable, while acute stress r eactions were inhibited or exogenously induced. Methods: Rats were adrenale ctomised. Subcutaneous corticosterone pellets maintained basal glucocortico id concentrations while acute changes were mimicked by corticosterone injec tions. Anxiety was assessed by the social interaction test. Temporal change s were evaluated by submitting rats to the same manipulations three times a t two-day intervals. Results: Buspirone applied to animals with stable and low plasma glucocorticoid concentrations induced a dramatic increase in soc ial interactions. A slight locomotor suppressive effect was also noticed. T he effects of buspirone proved to be stable over time in these animals. Acu te treatment with corticosterone doubled the locomotor suppressive effects of buspirone and reversed its anxiolytic effects: the buspirone-corticoster one combination was anxiogenic after the first application. During the seco nd and third treatment, the impact of corticosterone on buspirone efficacy gradually decreased, but the combined treatment remained about half as effe ctive in reducing anxiety as buspirone alone.