The changes in sympathetic innervations in lymphoid organs could be a key factor in immune dysregulation. The endocannabinoid system has been shown to exhibit potent immunomodulatory effects that may differ between males and females, representing a potential therapeutic target for peripheral and central inflammatory disorders. Thus, in the present study, an examination was made of the effect of fatty acid amide hydrolase inhibitor URB597 treatment on splenic catecholamine content, synthesis, uptake and degradation in chronically unpredictably stressed (CUS) female and male rats. The results show that CUS increases anxiety-like behaviors and that URB597 had an anxiolytic effect on chronically stressed animals of both sexes. CUS induced the expression of plasma interleukin – 6 (IL-6), interleukin – 10 (IL-10) and IL-6 in the spleen, whereas the expression of IL-10 was reduced in the spleen of both sexes. URB597 treatment did not cause changes in IL-6 in plasma or the spleen, whereas it increased IL-10 in the spleen in CUS animals of both sexes. CUS caused a significant depletion of noradrenaline content in the spleen of female rats and a reduction in noradrenaline uptake in the spleen of female rats, while stressed males had a small but insignificant decrease of splenic noradrenaline levels and an enhanced uptake. The FAAH inhibitor URB597 enhances reduced noradrenaline content, affecting its uptake directly at the level of the spleen. It gives rise to the possibility that endocannabinoids exert a neurorestorative effect on the sympathetic nerve system and cell-mediated immune responses in the spleen of chronically stressed rats.

淋巴器官中交感神经的变化可能是免疫失调的关键因素。已经显示，内源性大麻素系统表现出强大的免疫调节作用，在男性和女性之间可能有所不同，代表了周围和中枢性炎症性疾病的潜在治疗靶标。因此，在本研究中，研究了脂肪酸酰胺水解酶抑制剂URB597对慢性不可预测压力（CUS）雌性和雄性大鼠脾脏儿茶酚胺含量，合成，摄取和降解的影响。结果表明，CUS增加了焦虑样行为，URB597对男女双方长期处于压力状态的动物具有抗焦虑作用。CUS诱导脾脏中血浆白介素– 6（IL-6），白介素– 10（IL-10）和IL-6的表达，而IL-10的表达在两性脾脏中均降低。URB597处理不会引起血浆或脾脏中IL-6的改变，而在男女两性的CUS动物中，脾脏中的IL-10都会增加。CUS导致雌性大鼠脾脏中去甲肾上腺素含量显着减少，雌性大鼠脾脏中去甲肾上腺素摄取减少，而压力大的雄性脾脏去甲肾上腺素水平降低但不明显，并且摄取增加。FAAH抑制剂URB597增强去甲肾上腺素含量降低，直接影响其在脾脏中的摄取。内源性大麻素对慢性应激大鼠脾脏中的交感神经系统和细胞介导的免疫反应产生神经修复作用。