Institute of Psychopharmacology, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, J5, 68159, Mannheim, Germany.
Biol Sex Differ. 2024 Oct 15;15(1):78. doi: 10.1186/s13293-024-00655-7.
Adolescent social isolation (ASI) has profound long-term effects on behavioral and neural development. Despite this, the specific long-term impact of ASI during different adolescent stages and across sexes remain underexplored.
Our study addresses this gap by examining the effects of early- and late- adolescent social isolation on both male and female rats. Rats were either isolated (or group-housed) starting from PD 21 (early) or PD 42 (late) for three weeks and then rehoused into groups. In adulthood (PD 90), rats underwent a battery of tests: elevated plus-maze, open field, novel object recognition, social interaction and social recognition memory and hotplate tests. Finally, we analyzed oxytocin receptor binding in several regions in the brains of a second cohort of rats.
Both, male and female rats from the late adolescent social isolation (LASI) groups spent significantly less time interacting in the social interaction test. Additionally, we observed a general decrease in social recognition memory regardless of sex. Both male ASI groups demonstrated heightened thermal pain sensitivity, while the opposite was observed in early adolescent social isolation (EASI) female rats. In the brain, we observed changes in oxytocin receptor (OTR) binding in the paraventricular nucleus of the hypothalamus (PVN) and paraventricular nucleus of the thalamus (PVT) and central amygdala (CeA) with the largest changes in EASI and LASI female rats.
Our model demonstrates long-lasting alterations on behavior and oxytocin receptor binding levels following ASI providing insights into the long-term effects of ASI in a time- and sex-specific manner.
青少年社交隔离(ASI)对行为和神经发育有深远的长期影响。尽管如此,不同青少年阶段和性别之间 ASI 的具体长期影响仍未得到充分探索。
我们的研究通过检查早期和晚期青春期社交隔离对雄性和雌性大鼠的影响来解决这一差距。大鼠从 PD21(早期)或 PD42(晚期)开始分别被隔离(或群养)三周,然后重新群养。在成年期(PD90),大鼠接受一系列测试:高架十字迷宫、旷场、新物体识别、社交互动和社交识别记忆以及热板测试。最后,我们分析了第二组大鼠大脑中几个区域的催产素受体结合情况。
来自晚期青春期社交隔离(LASI)组的雄性和雌性大鼠在社交互动测试中互动时间明显减少。此外,无论性别如何,我们都观察到社交识别记忆普遍下降。两个雄性 ASI 组均表现出热痛敏感性增加,而早期青春期社交隔离(EASI)的雌性大鼠则相反。在大脑中,我们观察到下丘脑室旁核(PVN)和丘脑室旁核(PVT)以及中央杏仁核(CeA)中的催产素受体(OTR)结合发生变化,EASI 和 LASI 雌性大鼠的变化最大。
我们的模型表明,在行为和催产素受体结合水平上,AS 后会产生持久的改变,这为时间和性别特异性地了解 ASI 的长期影响提供了线索。