Sills T L, Greenshaw A J, Baker G B, Fletcher P J
Biopsychology Section, Centre for Addiction and Mental Health, Clarke Division, Toronto, Canada.
Behav Pharmacol. 2000 Apr;11(2):109-16. doi: 10.1097/00008877-200004000-00002.
The results of the present study show that 5 days of systemic treatment with fluoxetine (5 mg/kg) resulted in an augmented locomotor response to amphetamine (0.5 mg/kg). This augmented response to amphetamine was observed 24 and 48 h, but not 5 days, after the cessation of fluoxetine treatment. Subchronic fluoxetine treatment also produced an increase in the brain concentration of amphetamine when rats were challenged with amphetamine 48 h, but not 5 days, after the cessation of fluoxetine treatment. Thus, the effect of subchronic fluoxetine in augmenting amphetamine-induced hyperactivity was consistent with the effect of subchronic fluoxetine in augmenting the amphetamine concentration in the brain. This pattern of results indicates that subchronic fluoxetine potentiates the response to amphetamine within a limited time-window, and that this potentiating effect is likely to be due to the reduced metabolism of amphetamine via the inhibition of cytochrome P450 by fluoxetine and/or its metabolite norfluoxetine.
本研究结果表明，用氟西汀（5毫克/千克）进行5天的全身治疗会导致对苯丙胺（0.5毫克/千克）的运动反应增强。在停止氟西汀治疗后24小时和48小时观察到对苯丙胺的这种增强反应，但在5天后未观察到。当在停止氟西汀治疗后48小时而非5天用苯丙胺对大鼠进行激发时，亚慢性氟西汀治疗也会使大脑中苯丙胺的浓度增加。因此，亚慢性氟西汀增强苯丙胺诱导的多动的作用与亚慢性氟西汀增加大脑中苯丙胺浓度的作用一致。这种结果模式表明，亚慢性氟西汀在有限的时间窗口内增强对苯丙胺的反应，并且这种增强作用可能是由于氟西汀及其代谢产物去甲氟西汀通过抑制细胞色素P450而导致苯丙胺代谢减少所致。
