title: Comparison of the anticonflict effect of buspirone and its major metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) in rats.
abstract: The anxiolytic effects of buspirone and its major metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP) have been investigated with a conflict (shock-induced suppression of drinking) paradigm in rats. Buspirone (10 mg/kg, p.o.) showed an anticonflict activity with a bell-shaped dose-response relationship without any effect on spontaneous water consumption. Higher doses of buspirone reduced the punished response. Diazepam (20 and 40 mg/kg, p.o.) also showed an anticonflict activity in a dose-dependent manner, but animals with diazepam showed an increase in spontaneous water consumption at these doses. On the other hand, 1-PP (6.25-200 mg/kg, p.o.) showed a weak anticonflict activity with a significant effect at 25 mg/kg without any effect on spontaneous water consumption. In the 7-day treatment test, buspirone (5 and 10 mg/kg, p.o.), 1-PP (5 and 25 mg/kg, p.o.) and diazepam (10 and 40 mg/kg, p.o.) did not develop the tolerance to the anticonflict activity. Conversely, the anticonflict activity of diazepam was increased by the repeated treatment. Diazepam (10 mg/kg, p.o.) showed an anticonflict activity without any effect on spontaneous water consumption in this test. These results demonstrated that buspirone clearly exhibited an anticonflict effect similar to that of diazepam in a Vogel-type conflict test, and its real anxiolytic effect may not be always based on 1-PP, the main metabolite of buspirone.
authors.affiliation: Pharmacology Laboratory, Bristol-Myers Squibb K.K., Aichi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Amano
authors.forename: A
authors.initials: A
authors.lastname: Goto
authors.forename: A
authors.initials: A
authors.lastname: Sakai
authors.forename: M
authors.initials: M
authors.lastname: Achiha
authors.lastname: nee Hara
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.forename: C
authors.initials: C
authors.lastname: Hara
authors.forename: N
authors.initials: N
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002065:Buspirone / Q000031:analogs & derivatives* / Q000494:pharmacology; D003220:Conflict, Psychological; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D014151:Anti-Anxiety Agents; C037921:1-(2-pyrimidinyl)piperazine; D003975:Diazepam; D002065:Buspirone