Little is known about the mechanisms that promote divergence of function between left and right in the hippocampus, which is most affected by external factors and critical for spatial memory. We investigated the levels of memory-related mediators in the left and right hippocampus and spatial memory in rats exposed to predictable chronic stress (PCS) and an enriched environment (EE) during adolescence. Twenty-eight-day-old Sprague-Dawley rats were divided into control (standard cages), PCS (15 min/day immobilization stress for four weeks), and EE (one hour/day environmentally enriched cages for four weeks) groups. After the applications, spatial memory was tested with the Morris water maze, and the serum levels of corticosterone were evaluated. The levels of brain-derived neurotrophic factor (BDNF) and neuronal nitric oxide synthase (nNOS), which are critical for synaptic plasticity; malondialdehyde (MDA; lipid-peroxidation indicator); protein carbonyl (protein oxidation indicator); and superoxide dismutase (antioxidant enzyme) were evaluated in the left and right hippocampus. Corticosterone levels in both the PCS and EE groups did not change compared with control. In both the PCS and EE groups, spatial memory improved and BDNF was increased in both halves of the hippocampus, still there was an asymmetry. nNOS levels were increased in the dentate gyrus and CA1 regions of the right hippocampus in both PCS and EE groups. MDA levels were increased but PCO levels were decreased in the right hippocampus in both the PCS and EE groups, but SOD did not change in either half of the hippocampus. Our results suggest that both PCS and EE improved spatial memory by increasing BDNF and nNOS in the right hippocampus and that, interestingly; MDA could be the physiological signal molecule in the right hippocampus for spatial memory process.