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| 5-HT1A受体激动剂对青春期大鼠病理性攻击行为和前额叶皮质、海马内脑源性及胶质细胞源性神经营养因子的影响 |
| 蔡亚兰1,陈竹1,赵媛1,屈远1,秦光成2,陈力学2,胡华1* |
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(1. 重庆医科大学附属第一医院精神科, 重庆 400016;
2. 重庆医科大学附属第一医院实验研究中心, 重庆 400016
*通信作者) |
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| 摘要: |
| 目的 探索5-羟色胺1A（5-HT1A）受体激动剂8-OH-DPAT对青春期大鼠病理性攻击行为及对前额叶皮质、海马内脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF）的影响。方法 出生后21 d的雄性SD大鼠42只随机分为6组（n=7）：模型组、正常组、模型+药物组、模型+生理盐水（NS）组、正常+药物组、正常+NS组。模型组、模型+药物组及模型+NS组采用早年慢性应激建立病理性攻击模型，余3组正常饲养。建模成功后对模型+药物组、正常+药物组及模型+NS组、正常+NS组分别行2周的8-OH-DPAT（0.5 mg/kg）或生理盐水（2 mL/只）腹腔注射。用居住-入侵实验检测大鼠攻击行为，蛋白质印迹分析检测大鼠脑前额叶皮质及海马内BDNF、GDNF蛋白表达水平。结果 与正常组比较，模型组攻击潜伏期缩短（P<0.01）、攻击持续时间及攻击总数增加（P<0.01）。模型+药物组攻击潜伏期较模型+NS组延长（P<0.05）；模型+药物组攻击持续时间较正常+药物组增加（P<0.05）；药物干预后攻击总数组间比较差异无统计学意义（P>0.05）。模型组前额叶皮质、海马内BDNF及GDNF表达水平均低于正常组（P<0.01），模型+NS组较正常+NS组降低（P<0.05，P<0.01），模型+药物组较模型+NS组升高（P<0.05，P<0.01）。结论 前额叶皮质及海马内BDNF、GDNF可能与早年慢性应激所致青春期大鼠病理性攻击行为的发生有关。5-HT1A受体激动剂可上调前额叶皮质及海马内BDNF、GDNF的蛋白表达，并在一定程度上减轻早年慢性应激所致青春期大鼠病理性攻击行为。 |
| 关键词: 青春期 病理性攻击行为 5-HT1A受体 前额叶皮质 海马 脑源性神经营养因子 胶质细胞源性神经营养因子 |
| DOI：10.16781/j.0258-879x.2017.07.0885 |
| 投稿时间：2016-08-24修订日期：2017-03-02 |
| 基金项目:重庆市自然科学基金（CSTC，2011jjA10104），重庆医科大学国家自然科学预研资助项目（NSFYY201111）. |
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| Effect of serotonin 1A receptor agonist on pathological aggressive behaviors and brain-derived and glial cell-derived neurotrophic factors in prefrontal cortex and hippocampus of puberty rats |
| CAI Ya-lan1,CHEN Zhu1,ZHAO Yuan1,QU Yuan1,QIN Guang-cheng2,CHEN Li-xue2,HU Hua1* |
(1. Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;
2. Experimental Research Center, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
*Corresponding author) |
| Abstract: |
| Objective To explore the effect of serotonin 1A (5-HT1A) receptor agonist 8-OH-DPAT on pathological aggressive behavior, brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in prefrontal cortex and hippocampus in pubertal rats. Methods Forty-two 21-day-old male SD rats were randomly divided into 6 groups:model group, normal group, model+8-OH-DPAT group, model+normal saline (NS) group, normal+8-OH-DPAT group and normal+NS group, with 7 rats in each group. The rats in the model, model+8-OH-DPAT and model+NS groups were given a series of early chronic stresses to establish the pathological aggressive animal model, and the other 3 groups were fed normally. Then the rats in the model+8-OH-DPAT and normal+8-OH-DPAT groups were injected intraperitoneally with 8-OH-DPAT (0.5 mg/kg), while the rats in the model+NS and normal groups were administered with 2 mL of NS. We determined the aggressive behaviors of the rats through resident-intruder test and detected the protein expressions of BDNF and GDNF in prefrontal cortex and hippocampus by Western blotting. Results (1) Compared with the normal group, the latency in the first attack in the model group was significantly shorter (P<0.01), while duration of attack manifestations and total attacks were significantly higher (P<0.01). The latency of the first attack in the model+8-OH-DPAT group was significantly higher than that in the model+NS group (P<0.05); the duration of attack manifestations in the model+8-OH-DPAT group was significantly increased compared with the normal+8-OH-DPAT group (P<0.05); and there was no significant difference in the total attacks among the groups (P>0.05). (2) The protein expressions of BDNF and GDNF in the prefrontal cortex and hippocampus in the model group were significantly lower than those in the normal group (P<0.01), but they were significantly decreased in the model+NS group compared with the normal+NS group (P<0.05, P<0.01) and were significantly increased in the model+8-OH-DPAT group compared with the model+NS group (P<0.05, P<0.01). Conclusion The expressions of BDNF and GDNF in the prefrontal cortex and hippocampus may be related to the pathological aggressive behaviors induced by early chronic stress in puberty rats. 5-HT1A receptor agonist can reduce the pathological aggressive behaviors induced by early chronic stress and increase the expressions of BDNF and GDNF in prefrontal cortex and hippocampus in puberty rats. |
| Key words: pubterty pathological aggressive behavior 5-HT1A receptor prefrontal cortex hippocampus brain-derived neurotrophic factor glial cell line-derived neurotriophic factor |
