Sills T L, Greenshaw A J, Baker G B, Fletcher P J
Biopsychology Section, Clarke Institute of Psychiatry, Toronto, Canada.
Psychopharmacology (Berl). 1999 Feb;141(4):421-7. doi: 10.1007/s002130050852.
Amphetamine stimulates locomotor activity, in large part by activating central dopaminergic systems. Serotonin shares on overlapping distribution with dopamine and has been shown to modulate dopaminergic function and dopamine-mediated behaviors. The present study examined whether increasing serotonergic function, via the selective serotonin reuptake inhibitor fluoxetine, would alter the stimulatory effects of amphetamine on locomotor activity and dopamine overflow in the nucleus accumbens. In addition, the present study determined whether fluoxetine treatment would alter the metabolism of amphetamine. Results show that 5.0 mg/kg fluoxetine potentiated the locomotor activity induced by amphetamine (0.5-1.0 mg/ kg), and enhanced the increased dopamine overflow in the nucleus accumbens induced by amphetamine. Fluoxetine treatment also resulted in a higher concentration of amphetamine in the CNS. Together, these findings indicate that acute fluoxetine treatment potentiates the locomotor stimulating and dopamine activating effects of amphetamine. Further, the results indicate that fluoxetine potentiates the effects of amphetamine by decreasing the metabolism of amphetamine, probably through inhibition of cytochrome P450 isozymes.
苯丙胺刺激运动活性，很大程度上是通过激活中枢多巴胺能系统实现的。5-羟色胺与多巴胺分布重叠，且已被证明可调节多巴胺能功能及多巴胺介导的行为。本研究考察了通过选择性5-羟色胺再摄取抑制剂氟西汀增强5-羟色胺能功能，是否会改变苯丙胺对运动活性及伏隔核中多巴胺外溢的刺激作用。此外，本研究还确定了氟西汀治疗是否会改变苯丙胺的代谢。结果显示，5.0mg/kg氟西汀增强了苯丙胺（0.5-1.0mg/kg）诱导的运动活性，并增强了苯丙胺诱导的伏隔核中多巴胺外溢增加。氟西汀治疗还导致中枢神经系统中苯丙胺浓度更高。总之，这些发现表明急性氟西汀治疗增强了苯丙胺的运动刺激和多巴胺激活作用。此外，结果表明氟西汀可能通过抑制细胞色素P450同工酶来降低苯丙胺的代谢，从而增强苯丙胺的作用。
