Cognitive performance of juvenile monkeys after chronic fluoxetine treatment.
Cognitive performance of juvenile monkeys after chronic fluoxetine treatment.
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DOI：
10.1016/j.dcn.2017.04.008
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发表时间：
2017-08
影响因子：
4.7
通讯作者：
Roth RH
中科院分区：
文献类型：
--
作者：
Golub MS;Hackett EP;Hogrefe CE;Leranth C;Elsworth JD;Roth RH
当药物用于治疗儿童期抑郁和焦虑时，对大脑发育的潜在长期影响是一个问题。在这项研究中，雄性幼年恒河猴（三至四岁）接受了为期两年的氟西汀或溶剂（N = 16/组）给药。在给药后1年人道处死后进行的皮质树突棘组织形态学检查（N = 8/组）表明，氟西汀给药猴的前额叶皮质中存在树突棘突触密度增加的趋势。在给药期间，对受试者进行自动认知测试培训，并通过持续注意力测试进行评价。停药后，评价持续注意力、识别记忆和认知灵活性。氟西汀在给药期间和给药后均影响持续注意力，以遗漏错误为指标。在给药后识别记忆和认知灵活性测试中，氟西汀不影响反应准确性，但与溶剂对照组相比，先前氟西汀治疗的猴在测试期间错过了更多的试验启动和选择。药物治疗也与遗传和环境变量相互作用：MAOA基因型（高和低转录率多态性）和测试位置（上层或下层笼）。注意力的自上而下的皮质调节的改变可能与青少年氟西汀治疗后的认知测试表现的这种模式有关。
Potential long term effects on brain development are a concern when drugs are used to treat depression and anxiety in childhood. In this study, male juvenile rhesus monkeys (three-four years of age) were dosed with fluoxetine or vehicle (N = 16/group) for two years. Histomorphometric examination of cortical dendritic spines conducted after euthanasia at one year postdosing (N = 8/group) suggested a trend toward greater dendritic spine synapse density in prefrontal cortex of the fluoxetine-treated monkeys. During dosing, subjects were trained for automated cognitive testing, and evaluated with a test of sustained attention. After dosing was discontinued, sustained attention, recognition memory and cognitive flexibility were evaluated. Sustained attention was affected by fluoxetine, both during and after dosing, as indexed by omission errors. Response accuracy was not affected by fluoxetine in post-dosing recognition memory and cognitive flexibility tests, but formerly fluoxetine-treated monkeys compared to vehicle controls had more missed trial initiations and choices during testing. Drug treatment also interacted with genetic and environmental variables: MAOA genotype (high- and low transcription rate polymorphisms) and testing location (upper or lower tier of cages). Altered development of top-down cortical regulation of effortful attention may be relevant to this pattern of cognitive test performance after juvenile fluoxetine treatment.
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作者：
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