title: Tandospirone suppresses impulsive action by possible blockade of the 5-HT1A receptor.
abstract: Higher impulsivity is observed in several psychiatric disorders and could be a risk factor for drug addiction, criminal involvement, and suicide. Although the involvement of the 5-HT1A receptor in impulsive behavior has been indicated, the effects of clinically relevant drugs have been rarely tested. In the present study, we examined whether (3aR,4S,7R,7aS)-rel-hexahydro-2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-4,7-methano-1H-isoindole-1,3(2H)-dione hydrochloride (tandospirone), an anxiolytic and a partial agonist of the 5-HT1A receptor, could affect impulsive action in the 3-choice serial reaction time task. Rats were acutely administered tandospirone (0, 0.1, and 1 mg/kg, i.p.). Tandospirone decreased the number of premature responses, an index of impulsive action, in a dose-dependent manner. N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY100635; 0.3 mg/kg, s.c.), a 5-HT1A receptor antagonist, did not reverse the suppressing effects of tandospirone on impulsive action. Moreover, a higher dose of WAY100635 (1 mg/kg, s.c.) suppressed impulsive action without tandospirone. Thus the effects of tandospirone on impulsivity might be due to the antagonistic action. Tandospirone could be a therapeutic candidate for impulsivity-related disorders.
authors.affiliation: Department of Neuropharmacology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. gwd0701@yahoo.co.jp
authors.forename: Yu
authors.initials: Y
authors.lastname: Ohmura
authors.forename: Haruko
authors.initials: H
authors.lastname: Kumamoto
authors.forename: Iku
authors.initials: I
authors.lastname: Tsutsui-Kimura
authors.forename: Masabumi
authors.initials: M
authors.lastname: Minami
authors.forename: Takeshi
authors.initials: T
authors.lastname: Izumi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshida
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshioka
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007175:Impulsive Behavior / Q000188:drug therapy* / Q000209:etiology; D054833:Isoindoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014151:Anti-Anxiety Agents; D054833:Isoindoles; D010879:Piperazines; D011725:Pyridines; D011743:Pyrimidines; D058829:Serotonin 5-HT1 Receptor Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C055267:tandospirone; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide