Activation Of Extracellular Signal-Regulated Kinase-1and-2(ERK1/2) In Postnatal Period Regulates Adult Social Interaction Behavior In Rats

Objective:To explore the Spatial-temporal pattern of ERK1/2activation in rats’brain and its role in social interaction in adulthood.Methods:Phospho-ERK1/2is bio-mark of ERK1/2activation. Firstly, expression of pERK1/2in the medial prefrontal cortex and hippocampus at postnatal (PND)1、3、5、7、14、21、28、60day were explored with western blot. Then, the rats were injected subcutaneously with SL327(30mg/kg) to inhibit ERK1/2activation during peak time of pERK1/2expression. At adulthood, a three-chamber social interaction box was used to test social interaction. Open field test、the elevated plus maze and light-dark box were used to test anxiety-like behavior. Following behavioral test, glutamate receptors(GluR1、GluR2NMDA1R)、biomarker of excitatory and inhibitory synapse terminal(vGluT、vGAT)and PSD95in the medial prefrontal cortex and hippocampus were tested with western blotResult:In the medial prefrontal cortex, ERK1/2was activated at birth and increased significantly at postnatal day14(PND14) then decreased to the level as that at birth. While no significant alterations of pERK1/2was found in hippocampus. After treatment with SL327at the time of PND7-PND14, the rats showed deficit social preference and decreased social interaction behavior in the three-chamber social interaction test. Beside, the rats showed higher level of anxiety in elevated plus maze and light-dark box without alteration in locomotor activity. Western blot results showed that NMDA1R and PSD95decreased, while no alterations of GluRs and vGluT、vGAT in the medial prefrontal cortex. However, no alterations of those proteins were found except vGAT decrease in hippocampus.Conclusion:The peak of pERK1/2expression was observed at postnatal14days in the medial prefrontal cortex. Inhibition of ERK1/2activation during postnatal7-14days lead to impairment of social interaction in adulthood, which was probably associated with alteration expression of NMDA1R and PSD95.