Anticonflict action of tandospirone in a modified Geller-Seifter conflict test in rats.
Tandospirone is a novel non-benzodiazepine compound possessing potent anxiolytic properties in a water lick conflict paradigm in rats and a high affinity for central 5-HT1A receptors. In the present study, tandospirone was evaluated for anxiolytic activity in a modified Geller-Seifter conflict paradigm in rats. Tandospirone produced significant increases in the punished responding at doses of 1.25, 2.5 and 5.0 mg/kg, i.p. or 20 mg/kg, p.o., although it decreased unpunished responding at doses of 2.5 and 5.0 mg/kg, i.p. or 20 mg/kg, p.o. Likewise, diazepam was also effective after i.p.-administration in this test, and its minimum effective dose was slightly higher than that of tandospirone. This suggests that tandospirone might be as effective in the treatment of anxiety as diazepam. The anticonflict action of tandospirone was not inhibited by Ro-15-1788, a benzodiazepine antagonist, although that of diazepam was completely inhibited. 8-OH-DPAT, a full agonist of 5-HT1A receptors, was also effective in this test with a high potency. Therefore, the possibility exists that the anticonflict action of tandospirone is related to its agonist action on 5-HT1A receptors, not on benzodiazepine receptors.
Shimizu
H
H
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Kumasaka
Y
Y
Tanaka
H
H
Hirose
A
A
Nakamura
M
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D003220:Conflict, Psychological; D003975:Diazepam / Q000494:pharmacology; D004597:Electroshock; D005442:Flumazenil / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; D013764:Tetrahydronaphthalenes; C055267:tandospirone; D005442:Flumazenil; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003975:Diazepam