Department of Neuropharmacology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
J Pharmacol Sci. 2013;122(2):84-92. doi: 10.1254/jphs.12264fp. Epub 2013 May 24.
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.
在几种精神疾病中观察到更高的冲动性，并且可能是药物成瘾、犯罪参与和自杀的风险因素。尽管已经表明 5-HT1A 受体参与冲动行为，但很少测试临床相关药物的作用。在本研究中，我们检查了（3aR，4S，7R，7aS）-rel-六氢-2-[4-[4-（2-嘧啶基）-1-哌嗪基]丁基]-4,7-甲撑-1H-异吲哚-1,3（2H）-二酮盐酸盐（坦度螺酮），一种抗焦虑药和 5-HT1A 受体的部分激动剂，是否可以影响 3 选择连续反应时间任务中的冲动行为。大鼠急性给予坦度螺酮（0、0.1 和 1 mg/kg，ip）。坦度螺酮以剂量依赖性方式减少冲动行为的过早反应次数，这是冲动行为的一个指标。N-[2-[4-（2-甲氧基苯基）-1-哌嗪基]乙基]-N-2-吡啶基环己烷甲酰胺马来酸盐（WAY100635；0.3 mg/kg，sc），5-HT1A 受体拮抗剂，不能逆转坦度螺酮对冲动行为的抑制作用。此外，更高剂量的 WAY100635（1 mg/kg，sc）在没有坦度螺酮的情况下抑制冲动行为。因此，坦度螺酮对冲动性的影响可能归因于拮抗作用。坦度螺酮可能是治疗与冲动相关的疾病的候选药物。
