Stress exposure can lead to the precipitation of psychiatric disorders in susceptible individuals, but the molecular underpinnings are incompletely understood. We used forced swimming in mice to reveal stress-regulated genes in the CA3 area of the hippocampus. To determine changes in the transcriptional profile 4 h and 8 h after stress exposure microarrays were used in the two mouse strains C57BL/6J and DBA/2J, which are known for their differential stress response. We discovered a surprisingly distinct set of regulated genes for each strain and followed selected ones by in situ hybridisation. Our results support the concept of a phased transcriptional reaction to stress. Moreover, we suggest novel stress-elicited pathways, which comprise a number of genes involved in the regulation of neuronal plasticity. Furthermore, we focused in particular on dihydropyrimidinase like 2, to which we provide evidence for its regulation by NeuroD, an important factor for neuronal activity-dependent dendritic morphogenesis.