Atypical anxiolytic profile of buspirone and a related drug, SM-3997, in a modified forced swim test employing straw suspension.

Abstract

Previous reports have shown that immobility time increases in the presence of suspended straws in association with an inhibition of straw-climbing behavior after acute administration of a prototypical anxiolytic benzodiazepine (BZD) such as diazepam. In this modified forced swim (MFS) test employing straw suspension, the effects of two new non-BZD compounds were tested and compared with those of diazepam (0.5, 1, and 5 mg/kg, IP) used in a previous MFS test. After a 5-min test of forced swimming, four straws were suspended just above the surface of the water and subsequently the straw-climbing trials were counted for 5 min as an index of escape behaviors induced by negative emotionality (stress and/or anxiety). Rats were injected IP with either saline, buspirone HCl (0.5, 1, and 5 mg/kg), or a related compound, SM-3997 (5, 10, and 20 mg/kg), 30 min before testing. At lower doses, both buspirone (0.5, 1 mg/kg) and SM-3997 (5, 10 mg/kg) reduced the duration of immobility, as opposed to that of diazepam. Conversely, buspirone at the highest dose of 5 mg/kg significantly prolonged the duration of immobility, and SM-3997 at 20 mg/kg also prolonged its duration, indicating a biphasic effects. All doses of buspirone and SM-3997 inhibited straw-climbing counts, in the same manner as diazepam. These results suggest that buspirone may possess relatively weak and/or atypical anxiolytic effects at lower doses, whereas at 5 mg/kg this compound may have an anxiolytic effect. In addition, SM-3997 may be a less potent anxiolytic drug than buspirone in the MFS test following a single-injection protocol.