Fluoxetine and aripiprazole treatment following prenatal immune activation exert longstanding effects on rat locomotor response.
Fluoxetine and aripiprazole treatment following prenatal immune activation exert longstanding effects on rat locomotor response.
复制标题
产前免疫激活后的氟西汀和阿立哌唑治疗对大鼠运动反应产生长期影响。
DOI：
10.1016/j.physbeh.2012.02.004
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发表时间：
2012
影响因子：
2.9
通讯作者：
McNamara,RobertK
中科院分区：
文献类型：
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作者：
Richtand,NeilM;Ahlbrand,Rebecca;Horn,Paul;Tambyraja,Rabindra;Grainger,Molly;Bronson,StefanieL;McNamara,RobertK
目的在自然环境中进行的治疗干预研究表明，抗抑郁药和抗精神病药在改善首发精神病高危个体的临床结局方面可能同样有效。值得注意的是，在与精神病预防相关的小鼠产前免疫激活模型中，氟西汀治疗后观察到了有益和潜在的不良反应。我们试图通过研究氟西汀的影响，以及抗精神病药物阿立哌唑，在大鼠产前免疫activationmodel.METHODSPregnant Sprague-Dawley大鼠妊娠第14天注射聚I：C或生理盐水，以扩大这些发现。聚I：C和生理盐水处理母鼠的后代从出生后第35天至第70天接受氟西汀（10.0 mg/kg/d）、阿立哌唑（0.66 mg/kg/d）或溶剂。在三个月时测定了对新奇感、盐水注射和安非他明（1和5 mg/kg）的运动反应，即，氟西汀和阿立哌唑在3个月时对苯丙胺（1 mg/kg）的行为反应都有有益的作用，改善了产前免疫激活对聚I：C治疗的母鼠后代的影响。值得注意的是，这两种药物也产生了影响，在后代的控制（盐水处理）的母鼠对运动反应injection. CONCLUSIONSSFluoxetine和阿立哌唑预处理的聚I：C后代从出生后第35天至70天稳定的反应，持续通过3个月的年龄，类似的早期发现，在小鼠中，氟西汀治疗产前免疫激活后，防止改变运动反应安非他明。目前的数据还证实了早期的结果，即对照母鼠的后代在接受氟西汀和抗精神病药物治疗后可能出现不良行为影响，突出了在青春期发育过程中暴露于预防性药物治疗的治疗和安全性问题。需要进一步的研究来确定这些临床前发现的临床和流行病学后果。
AIMStudies characterizing treatment interventions in a naturalistic setting suggest that antidepressant and antipsychotic medications may be equally effective in improving clinical outcome in individuals at high risk for first-episode psychosis. Of interest, both beneficial as well as potentially adverse effects have been observed following fluoxetine treatment in a mouse prenatal immune activation model of relevance to psychosis prevention. We sought to extend those findings by examining the effects of fluoxetine, as well as the antipsychotic medication aripiprazole, in a rat prenatal immune activation model.METHODSPregnant Sprague–Dawley rats were injected with poly I:C or saline on gestational day 14. Offspring of poly I:C and saline-treated dams received fluoxetine (10.0mg/kg/d), aripiprazole (0.66mg/kg/d), or vehicle from postnatal days 35 to 70. Locomotor responses to novelty, saline injection, and amphetamine (1 and 5mg/kg) were determined at three months, i.e., 21days following drug discontinuation.RESULTSBoth fluoxetine and aripiprazole had beneficial effects on behavioral response to amphetamine (1mg/kg) at 3months, ameliorating the impact of prenatal immune activation on offspring of poly I:C-treated dams. Significantly, both drugs also exerted effects in offspring of control (saline-treated) dams on locomotor response to injection.CONCLUSIONSFluoxetine and aripiprazole pretreatment of poly I:C offspring from postnatal days 35 to 70 stabilized response to amphetamine exposure persisting through 3months of age, similar to earlier findings in mice that fluoxetine treatment following prenatal immune activation prevented altered locomotor response to amphetamine. The current data also confirm earlier findings of potential adverse behavioral effects in offspring of control dams following treatment with fluoxetine and antipsychotic medications, highlighting the potential for both therapeutic as well as safety concerns with exposure to preventive pharmacological treatments over the course of adolescent development. Further study is needed to determine clinical and epidemiological consequences of these pre-clinical findings.