Atypical anxiolytic profile of buspirone and a related drug, SM-3997, in a modified forced swim test employing straw suspension.
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.
Nishimura
H
H
Department of Pharmacology, Kurume University School of Medicine, Japan.
Tanaka
M
M
Tsuda
A
A
Gondoh
Y
Y
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002065:Buspirone / Q000494:pharmacology*; D007103:Immobilization; D054833:Isoindoles; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming
D014151:Anti-Anxiety Agents; D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; C055267:tandospirone; D002065:Buspirone