Zer-Aviv Tomer Mizrachi, Akirav Irit
Department of Psychology, University of Haifa, Haifa, 3498838, Israel.
Hippocampus. 2016 Jul;26(7):947-57. doi: 10.1002/hipo.22577. Epub 2016 Mar 15.
Women are more vulnerable to stress-related mental disorders than men and the naturally occurring fluctuation in estrogen that occur across the estrus cycle can dramatically influence the pathophysiology observed following traumatic events. It has been demonstrated that the endocannabinoid (eCB) system could represent a therapeutic target for the treatment of post-traumatic stress disorder (PTSD) in males. The current study aimed to examine the effects of exposure to a traumatic event and acute enhancement of eCB signaling on hippocampal-dependent learning and plasticity in male and female rats. Males and females were exposed to the single prolonged stress (SPS) model of PTSD (restraint, forced swim, and sedation) followed by acute administration of the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3 mg/kg). Females were in diestrus during SPS exposure. SPS exposure impaired extinction and hippocampal plasticity tested a week later in males and females. Sex differences were observed in the effects of URB597 on hippocampal plasticity of SPS-exposed rats. Also, URB597 normalized the SPS-induced upregulation in CB1 receptor levels in the amygdala, prefrontal cortex (PFC), and hippocampus in males. In females, URB597 normalized the SPS-induced up regulation in CB1 receptors in the amygdala and PFC, but not hippocampus. Our findings support the eCB system as a therapeutic target for the treatment of disorders associated to inefficient fear coping in males and females. There are differences in the hippocampal response of males and females to the enhancement of eCB signaling after intense stress suggesting sex differences in treatment efficacy. © 2016 Wiley Periodicals, Inc.
女性比男性更容易患与压力相关的精神障碍，并且在整个发情周期中自然发生的雌激素波动会极大地影响创伤事件后观察到的病理生理学。已经证明，内源性大麻素（eCB）系统可能是治疗男性创伤后应激障碍（PTSD）的治疗靶点。本研究旨在检查暴露于创伤事件和急性增强eCB信号对雄性和雌性大鼠海马依赖性学习和可塑性的影响。雄性和雌性大鼠暴露于PTSD的单次长时间应激（SPS）模型（束缚、强迫游泳和镇静），然后急性给予脂肪酸酰胺水解酶（FAAH）抑制剂URB597（0.3mg/kg）。雌性大鼠在SPS暴露期间处于间情期。SPS暴露损害了一周后对雄性和雌性大鼠进行测试的消退和海马可塑性。观察到URB597对SPS暴露大鼠海马可塑性的影响存在性别差异。此外，URB597使雄性大鼠杏仁核、前额叶皮质（PFC）和海马中SPS诱导的CB1受体水平上调恢复正常。在雌性大鼠中，URB597使杏仁核和PFC中SPS诱导的CB1受体上调恢复正常，但海马中未恢复正常。我们的研究结果支持eCB系统作为治疗与男性和女性恐惧应对效率低下相关疾病的治疗靶点。强烈应激后，雄性和雌性大鼠海马对eCB信号增强的反应存在差异，这表明治疗效果存在性别差异。©2016威利期刊公司。
