EN
BACKGROUND AND AIMS: The chronic mild stress (CMS) procedure induces depression-like symptoms in animals. In this model, rats subjected for a prolonged time to mild stressors gradually decrease their responsiveness to rewarding stimuli. This deficit can be effectively reversed by chronic antidepressant treatment. Apoptotic changes in the prefrontal cortex were shown in animal stress models, as well as degenerative changes, which are reversed by antidepressant treatment in depressed patients. We aimed to study the apoptotic signaling-related genes in the prefrontal cortex (PFC) of rats treated with imipramine (IMI) in CMS model. METHODS: First, we used the TaqMan Low Density Arrays to indentify genes in the three groups of Wistar rats: sham-saline; stressIMI-responders and stress-IMI-nonresponders (the sucrose intake score did not return to the control level). Then, these groups of rats and two additional ones (stress-saline and sham-IMI) were assessed in the PCR reactions with one TaqMan probe for detailed mRNA analysis of the identified genes. Finally, the levels of these proteins were assessed by Western Blot in all experimental groups. RESULTS: We found that CMS decreased the expression of Pmaip1 mRNA (by 18%) and the effect remained unchanged in rats nonresponding behaviorally to IMI treatment. Furthermore, in rats nonresponding to IMI treatment, the Rock1 mRNA was decreased by 40% vs. sham and IMI responding rats. However, at the Rock1 protein level its decreased expression was observed in both groups, the IMI nonresponding and IMI responding animals (by 22% and 29%, respectively). CONCLUSION: Our results suggest the involvement of apoptotic Pmaip1 and Rock1 genes in the process of response to IMI treatment in CMS model of depression in rats. Supported by statutory funds of the Institute of Pharmacology PAS and POIG.01.01.02-12-004/09-00 grant financed by European Regional Development Fund.