Borges-Aguiar Ana Cristina, Schauffer Luana Zanoni, de Kloet Edo Ronald, Schenberg Luiz Carlos
Department of Physiological Sciences, Health Science Center, Federal University of Espírito Santo, Brazil.
Division of Endocrinology, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Behav Brain Res. 2018 May 15;344:132-144. doi: 10.1016/j.bbr.2018.02.020. Epub 2018 Feb 18.
The present study examined whether early life maternal separation (MS), a model of childhood separation anxiety, predisposes to panic at adulthood. For this purpose, male pups were submitted to 3-h daily maternal separations along postnatal (PN) days of either the 'stress hyporesponsive period' (SHRP) from PN4 to PN14 (MS11) or throughout lactation from PN2 to PN21 (MS20). Pups were further reunited to conscious (CM) or anesthetized (AM) mothers to assess the effect of mother-pup interaction upon reunion. Controls were subjected to brief handling (15 s) once a day throughout lactation (BH20). As adults (PN60), rats were tested for the thresholds to evoke panic-like behaviors upon electrical stimulation of dorsal periaqueductal gray matter and exposed to an elevated plus-maze, an open-field, a forced swim and a sucrose preference test. A factor analysis was also performed to gain insight into the meaning of behavioral tests. MS11-CM rather than MS20-CM rats showed enhanced panic responses and reductions in both swimming and sucrose preference. Panic facilitations were less intense in mother-neglected rats. Although MS did not affect anxiety, MS11-AM showed robust reductions of defecation in an open-field. Factor analysis singled out anxiety, hedonia, exploration, coping and gut activity. Although sucrose preference and coping loaded on separate factors, appetite (adult weight) correlated with active coping in both forced swim and open-field (central area exploration). Concluding, whereas 3h-daily maternal separations during SHRP increased rat's susceptibility to experimental panic attacks, separations throughout lactation had no effects on panic and enhanced active coping.
本研究探讨了童年期分离焦虑模型——早期生活母体分离(MS)是否会导致成年期恐慌。为此,雄性幼崽在出生后(PN)的“应激低反应期”(SHRP,从PN4至PN14,即MS11)或整个哺乳期(从PN2至PN21,即MS20)每天接受3小时的母体分离。幼崽随后与清醒(CM)或麻醉(AM)的母亲重聚,以评估母婴互动对重聚的影响。对照组在整个哺乳期每天接受一次短暂处理(15秒,即BH20)。成年后(PN60),对大鼠进行电刺激导水管周围灰质背侧诱发恐慌样行为的阈值测试,并使其暴露于高架十字迷宫、旷场、强迫游泳和蔗糖偏好测试中。还进行了因子分析,以深入了解行为测试的意义。MS11-CM组而非MS20-CM组的大鼠表现出增强的恐慌反应,且游泳和蔗糖偏好均降低。在被母亲忽视的大鼠中,恐慌促进作用较弱。尽管MS不影响焦虑,但MS11-AM组在旷场中的排便显著减少。因子分析明确了焦虑、享乐、探索、应对和肠道活动等因素。尽管蔗糖偏好和应对负载在不同因子上,但食欲(成年体重)与强迫游泳和旷场(中央区域探索)中的主动应对相关。总之,在应激低反应期每天3小时的母体分离会增加大鼠对实验性恐慌发作的易感性,而整个哺乳期的分离对恐慌无影响,但会增强主动应对能力。