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

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(0.5mg/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.

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

Abstract] Objective To explore the effect of serotonin(5-HT)1A receptor agonist(8-OH-DPAT) on pathological aggression and brain-derived neurotrophic factor(BDNF),glial-derived neurotrophic factor( GDNF) in prefrontal cortex and hippocampus in puberty rats. Methods Forty-two 21-day-old male Sprague-Dawley rats were randomized into 6 groups:experimental group, control group ,experimental+8-OH-DPAT group, experimental+saline group,control+8-OH-DPAT group and control +saline group.Rats in experimental group, experimental+8-OH-DPAT group and experimental +saline group were given chronic stressors from early life for modelling,rats in other three groups only grew up normally.After the modeling ,8-OH-DPAT( 0.5mg/kg) or saline (2ml/per) were respectively injected to the rats in experimental +8-OH-DPAT group,control+8-OH-DPAT group and experimental+saline group , control+saline group for two weeks.Resident-intruder test and Western Blot were used to test aggression and BDNF,GDNF, respectively.Results (1)Aggression: the latency to first attack,the duration of attack and the total attacks in experimental group were significant difference compared with the control group (P < 0.01).After the treatment of 8-OH-DPAT or saline ,compared with the experimental+saline group,the latency to first attack of experimental +8-OH-DPAT group significantly prolonged (P < 0.05),there was no significant difference among other groups (P > 0.05); experimental+8-OH-DPAT group was still significantly increased in the duration of attack compared with the control+8-OH-DPAT group (P < 0.05), there was no significant difference among other groups; For the total attacks, no obvious difference was found after treatment among four groups (P > 0.05).(2) BDNF, GDNF: both BDNF and GDNF in the prefrontal cortex and hippocampus of experimental group were relatively lower than control group (P < 0.01),but after the administration, both of them were significantly increased compared with the experimental+saline group (P < 0.05), no significant difference was discovered among other groups (P > 0.05). Conclusions (1) The BDNF and GDNF in the prefrontal cortex and hippocampus may be in relation to the pathological aggressive behaviors induced by early chronic stressors of puberty rats.(2) 5-HT1A receptor agonist can increase BDNF, GDNF in prefrontal cortex and hippocampus and to a certain extent reduce the pathological aggressive behavior induced by early life chronic stress on puberty rats.