Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town 7925, South Africa.
Brain Res. 2012 Oct 22;1480:61-71. doi: 10.1016/j.brainres.2012.07.013. Epub 2012 Sep 10.
BACKGROUND: Rats subjected to maternal separation display behavioral alterations (e.g. increased immobility in the forced swim test) and molecular changes (e.g. in growth factors and related signal transduction proteins). Light treatment has previously been shown to have antidepressant effects in rat models of depression, but has not been studied in a rodent model of maternal separation. METHODS: This study focused on maternally separated rat pups. The aim of this study was to compare the effects of chronic constant light exposure during adolescence with the selective serotonin reuptake inhibitor (SSRI), escitalopram. Behavioral changes (exploratory activity in the open field and elevated plus maze, 22 kHz ultrasonic vocalizations, immobility in the forced swim test) and molecular changes (brain-derived neurotrophic factor (BDNF), mitogen-activated protein kinase phosphatase-1 (MKP-1) in the ventral hippocampus, and mu-opioid receptors in the nucleus accumbens) were measured. RESULTS: Animals that had been subjected to maternal separation displayed an increased number and duration of 22 kHz vocalizations, increased immobility in the forced swim test, increased hippocampal BDNF, and decreased mu-opioid receptor levels in the nucleus accumbens in adulthood compared to controls. MKP-1 levels in the ventral hippocampus were not affected. After chronic light treatment, there was normalization of ultrasonic vocalizations, immobility on the forced swim test, and mu-opioid receptor levels in the nucleus accumbens. Chronic saline treatment reduced anxiety-like behavior and immobility in the forced swim test. Escitalopram did not have any significant effect in this rat model of depression. CONCLUSION: Chronic constant light treatment reversed a number of the behavioral and molecular effects of maternal separation. Light-induced up-regulation of mu-opioid receptors in the nucleus accumbens may play a key role in mediating such effects.
背景:经历过母体分离的大鼠表现出行为改变(例如,在强迫游泳试验中增加不动性)和分子变化(例如,生长因子和相关信号转导蛋白)。光照治疗先前已被证明在大鼠抑郁模型中具有抗抑郁作用,但尚未在母体分离的啮齿动物模型中进行研究。
方法:本研究集中在经历过母体分离的幼鼠上。本研究的目的是比较青春期慢性持续光照暴露与选择性 5-羟色胺再摄取抑制剂(SSRI)依地普仑的作用。行为变化(旷场和高架十字迷宫中的探索性活动、22 kHz 超声发声、强迫游泳试验中的不动性)和分子变化(脑源性神经营养因子(BDNF)、丝裂原活化蛋白激酶磷酸酶-1(MKP-1)在腹侧海马体中的变化,以及在伏隔核中的μ-阿片受体)进行了测量。
结果:与对照组相比,经历过母体分离的动物在成年后表现出 22 kHz 发声次数和持续时间增加、强迫游泳试验中不动性增加、海马体 BDNF 增加以及伏隔核中μ-阿片受体水平降低。腹侧海马体中的 MKP-1 水平没有受到影响。慢性光照治疗后,超声发声、强迫游泳试验中的不动性以及伏隔核中的μ-阿片受体水平得到了正常化。慢性盐水处理减少了焦虑样行为和强迫游泳试验中的不动性。依地普仑在这种抑郁大鼠模型中没有任何显著作用。
结论:慢性持续光照治疗逆转了母体分离的许多行为和分子影响。光诱导的伏隔核中μ-阿片受体的上调可能在介导这种作用中发挥关键作用。
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