Background: Chronic stress is known to induce hippocampal neuronal loss which can lead to depression disorders in humans (1). Stress-induced hippocampal damage is believed to be related to the neurotoxic activity of glucocorticoid hormones (2), however the intracellular mechanisms of this action are still obscure. We had studied the effects of repeated restraint stress on the mRNA expression of factors, related to the neuronal survival and viability: Bcl-2 (anti-apoptotic factor), mamallian target of rapamycin (mTOR) and proteasome subunits β5 and β9 (PSM). mTOR stimulates mRNA translation through phosphorylation of some translation factors (4E-BP1, p70S6K, rpS6) thus coordinating cell growth and neuroplasticity (3). Methods: Male Wistar rats (230-250 gr) underwent 4 hour of restraint stress in plastic tubes once per day for 10 days. Bcl-2, mTOR, PSM5β and PSM9β mRNA expression were studied in left-side hippocampus at the end of the experiments using real-time RT-PCR technique. Right hippocampus of each animal were immunohistochemically studied and the amount of NeuN-positive neuronal cells were measured in order to estimate the degree of neuronal loss. Numeric data are presented as mean±S.E.M, statistical significance as false-positive probabilities (p) computed using Student’s t-test and Student’s distribution. Results: Chronic restraint led to a significant body mass loss (-5.9% compared to +4.0% gain in control group), 1.5-fold increase in adrenal gland weight and thymic atrophy. Restraint also resulted in significant neuronal loss in hippocampus: amount of NeuN-positive cells were reduced from 195.4±4.0 cells per mm (N=35) to 172.1±3.1 cells per mm (N=21) in CA1 area; from 198.7±10.5 (N=16) to 141.6±6.9 (N=22) cells per mm in CA2 and from 156.2±5.4 (N=31) to 104.9±17.7 (N=16) cells per mm in CA3. Average Bcl-2 mRNA levels in hippocampus of chronically stressed rats were significantly elevated from 5.97±0.29 (N=11) to 8.88±0.29 (N=11) c.u. (p < 0.001). This was accompanied by the increase in mTOR mRNA levels from 3.15±0.23 (N=8) to 3.85±0.13 (N=8) c.u. (p < 0.05) what goes in line with the data obtained by (3), who observed increase in mTOR activity in response to a traumatic stress. PSMβ5 mRNA levels did not undergo significant changes while PSMβ9 expression was 1.5-times enhanced from 4.81±0.39 (N=8) to 7.47±1.03 (N=8) c.u. (p < 0.05). Conslusion: Together, these results suggest that changes in bcl2 pathways, mRNA translation and protein degradation may be the mechanisms contributing to the neuronal loss caused by chronic restraint stress.