RESUMO
Objective To better understand the role of CREB signaling pathway in chronic mild stress (CMS), we investigated the alteration of CREB and p-CREB in CMS rats with and without fluoxetine hydrochloride. Methods Fifty adult male Sprague-Dawley rats were randomly divided into three groups:CMS group (26), fluoxtine group (12) and con-trol group (12). The rats in CMS group and fluoxtine group received 8 weeks of chronic mild stress. Rats in fluoxtine group were administered daily injections of fluoxetine 10mg/kg I.P. Sucrose preference tests and open-field test were car-ried out after the 8th week. Based on endpoint sucrose-intake, animals were further divided into 4 groups:CMS sensitive group, CMS resilient group, fluoxtine group and control group. Western blot was used to detect the expression levels of CREB and p-CREB in the hippocampus and prefrontal cortex. Results The sucrose consumption was significantly de-creased in CMS resilience group compared to sensitive group, control group and fluoxetine-intervention group (all P<0.05). Similarly, the numbers in total arm entries, percentage of entries into open arms and time spent in open arms was significantly lower in CMS resilience group compared to control group(all P<0.05), but not different compared to CMS sensitive group(all P<0.05). The p-CREB in the hippocampus was significantly lower in CMS sensitive rat compared to CMS resilience group, control group and fluoxetine-intervention group(all P<0.05), but CREB was not dfferent among the four groups(all P<0.05). Conclusions The elevated phosphorylation of CREB in the hippocampus and prefrontal cortex of resilience CMS rats may contribute to the mood alteration induced by stress.