Csilla Leveleki

The effect of social factors on the anxiolytic efficacy of buspirone in male rats, male mice, and men

Earlier findings suggest that housing conditions in laboratory animals and life events in humans influence the efficacy of anxiolytic drugs. Here we report on the impact of social isolation on buspirone efficacy in male mice and rats as assessed by the elevated plus-maze. In addition, the impact of social support on buspirone efficacy was assessed in male patients. When administered 30 min before testing and irrespective of housing conditions, buspirone significantly suppressed locomotor activity both in mice (6 mg/kg) and rats (10 mg/kg) and, as such, other behavioral changes observed at this time point must be seen as behaviorally nonselective. However, these locomotor disruptive effects of buspirone were not evident in either species at longer injection-test intervals (2 and 4 h). When given 2 h prior to testing, a low (3 mg/kg) but not high (10 mg/kg) dose of buspirone increased the frequency of open arm exploration in rats (but not mice) irrespective of housing conditions. At the longest injection-test interval used (4 h), buspirone increased the duration of open arm exploration in individually housed, but not group-housed, rats. Similar, though somewhat less robust, effects were observed in male mice at this time. In a double-blind placebo-controlled study with male patients, chronic buspirone treatment (3 x 10 mg daily for 6 weeks) produced a highly significant reduction in scores on the Hamilton Rating Scale for Anxiety (HAM-A). Multiple regression analysis of social support received by patients indicated that the support of nonrelatives (but not of family or other relatives) was a strong positive predictor of buspirone efficacy. Taken together, our data support the hypothesis that social conditions affect the anxiolytic efficacy of buspirone. Results are discussed in relation to differences in the social organization of the three species investigated.

The effect of glucocorticoids on the anxiolytic efficacy of buspirone

Abstract. Rationale: The serotonergic system and the hypothalamus–hypophysis–adrenocortical axis reciprocally influence each other. Therefore, the interaction between stress and serotonergic anxiolytics should be of major concern for both laboratory investigations and clinical treatment. Objectives: We have studied the effects of the serotonergic anxiolytic buspirone in rats in which basal levels of glucocorticoids were low and stable, while acute stress reactions were inhibited or exogenously induced. Methods: Rats were adrenalectomised. Subcutaneous corticosterone pellets maintained basal glucocorticoid concentrations while acute changes were mimicked by corticosterone injections. Anxiety was assessed by the social interaction test. Temporal changes were evaluated by submitting rats to the same manipulations three times at two-day intervals. Results: Buspirone applied to animals with stable and low plasma glucocorticoid concentrations induced a dramatic increase in social interactions. A slight locomotor suppressive effect was also noticed. The effects of buspirone proved to be stable over time in these animals. Acute treatment with corticosterone doubled the locomotor suppressive effects of buspirone and reversed its anxiolytic effects: the buspirone–corticosterone combination was anxiogenic after the first application. During the second and third treatment, the impact of corticosterone on buspirone efficacy gradually decreased, but the combined treatment remained about half as effective in reducing anxiety as buspirone alone.