Kafetzopoulos V, Kokras N, Katsaitis Filippos, Sousa N, Leite-Almeida H, Sotiropoulos I, Dalla C
Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias St, Athens, 11527, Greece.
Department of Psychiatry, Medical School, University of Cyprus, Nicosia, Cyprus.
Psychopharmacology (Berl). 2024 Aug 20. doi: 10.1007/s00213-024-06667-w.
Depression is a serious psychiatric disease, which is diagnosed twice as frequently in women than men. We have recently shown that lesioning or inactivation of the nucleus reuniens (RE), which interconnects the prefrontal cortex (PFC) and hippocampus, promoted resilience to stress in males, exerts an antidepressant effect in the Forced Swim Test (FST) and prevents the development of behavioral and neurobiological alterations induced by the chronic mild stress model of depression.
In this study, we expand our findings on the FST in female rats and we investigate whether RE lesion presents sex differences following treatment with two distinct antidepressants, a selective serotonin reuptake inhibitor, i.e. sertraline and a tricyclic antidepressant, i.e. clomipramine.
Male and female rats received either a surgical lesion of the RE or sham operation, then treated with vehicle, sertraline (10mg/kg) or clomipramine (10mg/kg) and were subjected to the FST. Activation of key brain areas of interest (PFC, Hippocampus and RE) were measured by c-Fos immunoreactivity.
RE lesion induced an antidepressant-like phenotype in both female and male rats, confirming its crucial role in the stress response. Similarly to RE lesion, sertraline treatment resulted in increased swimming and decreased immobility duration, as well as enhanced head shake frequency, in both sexes. Notably, climbing behavior was increased only following clomipramine treatment. RE area was less active in females compared to male rats and in clomipramine-treated males compared to their corresponding vehicle-group. Activation of the PFC and the CA1 hippocampal area was reduced in clomipramine-treated females, in comparison to vehicle-treated female rats. This effect was not evident in males, which exhibited less activation in the PFC and the hippocampus than females.
Re lesion proves equally effective in female and male rats, but sex is highlighted as a pivotal factor in behavioral and treatment response in FST, as well as in related circuit connectivity and activation.
抑郁症是一种严重的精神疾病，女性的诊断率是男性的两倍。我们最近发现，损毁或使连接前额叶皮质（PFC）和海马体的 reuniens 核（RE）失活，可增强雄性对压力的恢复力，在强迫游泳试验（FST）中发挥抗抑郁作用，并防止由慢性轻度应激抑郁模型诱导的行为和神经生物学改变的发展。
在本研究中，我们扩展了对雌性大鼠 FST 的研究结果，并调查在用两种不同的抗抑郁药（一种选择性 5-羟色胺再摄取抑制剂，即舍曲林和一种三环类抗抑郁药，即氯米帕明）治疗后，RE 损毁是否存在性别差异。
雄性和雌性大鼠接受 RE 的手术损毁或假手术，然后用溶剂、舍曲林（10mg/kg）或氯米帕明（10mg/kg）治疗，并进行 FST。通过 c-Fos 免疫反应性测量感兴趣的关键脑区（PFC、海马体和 RE）的激活情况。
RE 损毁在雌性和雄性大鼠中均诱导出抗抑郁样表型，证实了其在应激反应中的关键作用。与 RE 损毁类似，舍曲林治疗导致两性的游泳时间增加、不动时间减少以及摇头频率增加。值得注意的是，仅在氯米帕明治疗后攀爬行为增加。与雄性大鼠相比，雌性大鼠的 RE 区域活性较低；与相应的溶剂组相比，氯米帕明治疗的雄性大鼠的 RE 区域活性较低。与溶剂治疗的雌性大鼠相比，氯米帕明治疗的雌性大鼠的 PFC 和海马体 CA1 区域的激活减少。这种效应在雄性中不明显，雄性的 PFC 和海马体的激活比雌性少。
RE 损毁在雌性和雄性大鼠中同样有效，但性别被视为 FST 中行为和治疗反应以及相关回路连接性和激活的关键因素。
