Effect Of 5-HT1A Receptor Agonist On Pathological Aggressive Behaviors And The ERK-CREB Pathway In Prefrontal Cortex In Puberty Rats

OBJECTIVETo explore target pathway of the effect of 5-HT1A receptor agonist on the pathological aggressive behaviors of puberty rats, by investigating the effect of 5-HT1A receptor agonist on pathological aggressive behaviors and the ERK-CREB pathway in prefrontal cortex in puberty rats.METHODSSixty-four male rats were randomly divided into model group, control group, control+saline group, model+saline group, control+8-OH-DPAT group and model+8-OH-DPAT group. On the twenty-one day after birth the model group, model+saline group and model+8-OH-DPAT group rats had suffered from the chronic stress of social isolation, reverse night and day, social stimulate and resident-intruder confrontations until puberty. The other group rats only grow up normally. The control+8-OH-DPAT group and model+8-OH-DPAT group rats received the treatment (8-OH-DPAT, 0.5mg/kg i.p.) for 7 days, the control+saline group, model+saline group rats received the same volume saline for 7days as control group. Resident-intruder experiment was performed to observe the variation of pathological aggressive behaviors of SD rats. Western Blot was used to test the biological indicator in prefrontal cortex.RESULTS1. Aggressive Behavioral test before treatment:Resident-intruder test: the pathological aggressive behaviors were significant increased in model group. The latency of aggression in model group was significant decreased in model group compare with control group (P<0.01), and the other aggressive indicators were increased (P<0.01).2.Aggressive Behavioral test after treatment:Resident-intruder test:the pathological aggressive behaviors of model+8-OH-DPAT group rats were significant decreased compare with model+saline group, the latency of aggression was increased and the persistence attack after intruder displays submissive and attack the vulnerable parts were decreased compare with model+saline group (p<0.05; p<0.05; p<0.01). But the aggression still higher than control+saline group and control+8-OH-DPAT group rats. The aggression behaviors of model+saline group still significant lower the control+saline group and control+8-OH-DPAT group rats (p<0.01). The aggression behaviors between the control+saline group and control+8-OH-DPAT group rats were no difference.3.Biological test in the prefrontal cortex before treatment:Western Blot showed that the level of p-ERK/ERK and p-CREB/CREB was decreased in model group rats compare with control group (p<0.05; p<0.01).4.Biological test in the prefrontal cortex after treatment:Western Blot showed that The level of p-ERK/ERK in model+8-OH-DPAT group rats was significant increased compare with model+saline group and decreased compare with control+8-OH-DPAT group (p<0.01;p<0.05).The level of p-ERK/ERK in model+saline group rats was decreased compare with control+saline group and control+8-OH-DPAT group (p<0.05;p<0.01). The level of p-ERK/ERK in control+8-OH-DPAT group rats was increased compare with control+saline group(p<0.05). The level of p-CREB/CREB in model+8-OH-DPAT group rats was significant increased compare with model+saline group (p<0.01),but no difference compare with control+saline group and control+8-OH-DPAT group. The level of p-CREB/CREB in model+saline group rats was significant decreased compare with other three group (p<0.01).The level of PCREB/CREB is no difference between control+8-OH-DPAT group and control+saline group.CONCLUSIONS1. The ERK and CREB in the prefrontal cortex have involved in the pathological aggressive behaviors of puberty rats.2.5-HT1A receptor agonist can reduce the pathological aggressive behaviors of puberty rats induced by early life chronic stress.3.5-HT1A receptor agonist can increase the phosphorylation of ERK and CREB in prefrontal cortex of puberty rats.These results suggest that the ERK and CREB in the prefrontal cortex have involved in the pathological aggressive behaviors of puberty rats and the ERK-CREB pathway in the prefrontal cortex maybe the target pathway of 5-HT1A agoinst reducing the pathological aggressive behaviors of puberty rats.