Selective serotonin reuptake inhibitors, fluoxetine and paroxetine, attenuate the expression of the established behavioral sensitization induced by methamphetamine
Selective serotonin reuptake inhibitors, fluoxetine and paroxetine, attenuate the expression of the established behavioral sensitization induced by methamphetamine
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DOI：
10.1038/sj.npp.1301111
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发表时间：
2007-03-01
影响因子：
7.6
通讯作者：
Nishikawa, Toru
中科院分区：
文献类型：
--
作者：
Kaneko, Yujiro;Kashiwa, Atsushi;Nishikawa, Toru
为了深入了解一种新的药物治疗方法的发展，以防止精神兴奋剂诱导的精神病和精神分裂症的治疗抵抗性复发，我们在小鼠中研究了选择性血清素再摄取抑制剂（SSRI）、氟西汀（FLX）和帕罗西汀（PRX）对甲基苯丙胺（MAP）诱导的已建立的致敏性的影响，甲基苯丙胺（MAP）是这些精神病复发的模型。因为据报道，大脑中血清素能传递的改变可以对抗致敏现象。与先前的报道一致，重复MAP治疗（每天1.0 mg/ kg，皮下注射）10天，在停药后第12天或第29天，MAP攻药剂量（0.24 mg/ kg，皮下注射）对运动活动的影响持续增强。在停止重复给药后12 - 16天每天注射FLX （10 mg/ kg, s c）或PRX (8 mg/ kg, s c)，可显著减弱MAP预处理在SSRI注射后13天增强兴奋剂激发剂量的运动反应的能力。反复使用FLX或PRX单独治疗后，13天后生理盐水和MAP刺激后的运动刺激均未受到影响。提示间歇性、重复性血清素能张力升高可能抑制MAP预处理所致运动致敏的表达。提示临床可用的5 -羟色胺再摄取抑制剂可用于预防药物性精神病和精神分裂症幻觉偏执状态的复发。
To obtain an insight into the development of a new pharmacotherapy that prevents the treatment- resistant relapse of psychostimulant-induced psychosis and schizophrenia, we have investigated in the mouse the effects of selective serotonin reuptake inhibitors ( SSRI), fluoxetine ( FLX) and paroxetine ( PRX), on the established sensitization induced by methamphetamine ( MAP), a model of the relapse of these psychoses, because the modifications of the brain serotonergic transmission have been reported to antagonize the sensitization phenomenon. In agreement with previous reports, repeated MAP treatment ( 1.0 mg/ kg a day, subcutaneously ( s.c.)) for 10 days induced a long- lasting enhancement of the increasing effects of a challenge dose of MAP ( 0.24 mg/ kg, s. c.) on motor activity on day 12 or 29 of withdrawal. The daily injection of FLX ( 10 mg/ kg, s. c.) or PRX ( 8 mg/ kg, s. c.) from 12 to 16 days of withdrawal of repeated MAP administration markedly attenuated the ability of the MAP pretreatment to augment the motor responses to the challenge dose of the stimulant 13 days after the SSRI injection. The repeated treatment with FLX or PRX alone failed to affect the motor stimulation following the challenge of saline and MAP 13 days later. These results suggest that the intermittent and repetitive elevation of serotonergic tone may inhibit the expression of the motor sensitization induced by pretreatment with MAP. It is proposed that clinically available serotonin reuptake inhibitors could be useful for preventing the recurrence of hallucinatory-paranoid state in drug-induced psychosis and schizophrenia.