Inbred C57BL/6J (C57) and DBA/2J (DBA) mice were subjected to open-field evaluation and Porsolt swim test after restraint stress. Norepinephrine (NE) uptake sites in the locus coeruleus (LC) of these inbred mice were studied by using [3H]-tomoxetine. Results showed that naive C57 mice were more active in the open field and possessed more NE uptake sites in the LC than naive DBA mice. Previous work has shown that restraint decreases open field activity in C57 mice, but not DBA mice, whereas the present study has demonstrated that, after restraint stress, C57 mice spent more time immobile than DBA mice did in the forced swim test. Furthermore, in these stressed animals, NE uptake sites in the LC were greatly increased with consistently more uptake sites in C57 mice. Collectively, results of this study and the literature suggest that enhanced NE function in the LC of C57 mice is associated with their susceptibility to stress-induced behavioral depression.