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不同养育方式下幼年雄性恒河猴(Macaca mulatta)多巴胺系统的行为神经内分泌学。

The behavioral neuroendocrinology of dopamine systems in differently reared juvenile male rhesus monkeys (Macaca mulatta).

机构信息

Department of Anthropology, Emory University, 207 Anthropology Building, 1557 Dickey Drive, Atlanta, GA 30322-1003, United States; Center for Behavioral Neuroscience and Yerkes National Primate Research Center, Emory University, 954 Gatewood Rd. NE, Atlanta, GA 30322-0001, United States.

Center for Behavioral Neuroscience and Yerkes National Primate Research Center, Emory University, 954 Gatewood Rd. NE, Atlanta, GA 30322-0001, United States; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322-1003, United States.

出版信息

Horm Behav. 2022 Jan;137:105078. doi: 10.1016/j.yhbeh.2021.105078. Epub 2021 Nov 22.

Abstract

Dopamine (DA) is a critical neuromodulator of behavior. With propensities for addiction, hyper-activity, cognitive impairment, aggression, and social subordinance, monkeys enduring early maternal deprivation evoke human disorders involving dopaminergic dysfunction. To examine whether DA system alterations shape the behavioral correlates of adverse rearing, male monkeys (Macaca mulatta) were either mother-reared (MR: N = 6), or separated from their mothers at birth and nursery-reared (NR: N = 6). Behavior was assessed during 20-minute observations of subjects interacting with same- or differently-reared peers. Cerebrospinal fluid (CSF) biogenic amines, and serum testosterone (T), cortisol (CORT), and prolactin (PRL) were collected before and after pharmacologic challenge with saline or the DA receptor-2 (DRD2) antagonist Raclopride (RAC). Neuropeptide correlations observed in MR were non-existent in NR monkeys. Compared to MR, NR showed reduced DA tone; higher basal serum T; and lower CSF serotonin (5-HT). RAC increased PRL, T and CORT, but the magnitude of responses varied as a function of rearing. Levels of PRL significantly increased following RAC in MR, but not NR. Elevations in T following RAC were only significant among MR. Contrastingly, the net change (RAC CORT - saline CORT) in CORT was greater in NR than MR. Finally, observations conducted during the juvenile phase in a novel play-arena revealed more aggressive, self-injurious, and repetitive behaviors, which negatively correlated with indexes of dopaminergic tone in NR monkeys. In conclusion, early maternal deprivation alters brain DA systems, and thus may be associated with characteristic cognitive, social, and addiction outcomes.

摘要

多巴胺(DA)是行为的关键神经调节剂。具有成瘾倾向、过度活跃、认知障碍、攻击性和社会从属,经历早期母婴分离的猴子会引发涉及多巴胺能功能障碍的人类疾病。为了研究 DA 系统改变是否塑造了不良养育的行为相关性,雄性猴子(Macaca mulatta)要么由母亲抚养(MR:N=6),要么在出生时与母亲分离并在托儿所抚养(NR:N=6)。在观察对象与同养或异养同伴互动的 20 分钟期间,评估行为。在接受生理盐水或 DA 受体-2(DRD2)拮抗剂 Raclopride(RAC)的药物挑战前后,收集脑脊液(CSF)生物胺和血清睾酮(T)、皮质醇(CORT)和催乳素(PRL)。在 MR 中观察到的神经肽相关性在 NR 猴子中不存在。与 MR 相比,NR 显示出较低的 DA 张力;基础血清 T 较高;CSF 血清素(5-HT)较低。RAC 增加了 PRL、T 和 CORT,但反应的幅度因养育方式而异。在 MR 中,RAC 后 PRL 水平显著升高,但 NR 中没有。RAC 后 T 的升高仅在 MR 中具有统计学意义。相比之下,CORT 的净变化(RAC CORT-生理盐水 CORT)在 NR 中大于 MR。最后,在新的游戏竞技场中进行的青少年阶段观察显示出更具攻击性、自残和重复性的行为,这些行为与 NR 猴子的多巴胺能张力指标呈负相关。总之,早期母婴分离改变了大脑的 DA 系统,因此可能与认知、社会和成瘾的特征性结果相关。

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