Memory impairments of DBA/2J mice have been frequently reported in spatial and emotional behavior tests. However, in some memory tests involving food reward, DBA/2J mice perform equally well to C57BL/6J mice or even outperform them. Thus, it is conceivable that motivational factors differentially affect cognitive performance of different mouse strains. Therefore, spatial memory of DBA/2J and C57BL/6J mice was investigated in a modified version of the Barnes maze (mBM) test with increased complexity. The modified Barnes maze test allowed using either aversive or appetitive reinforcement, but with identical spatial cues and motor requirements. Both mouse strains acquired spatial learning in mBM tests with either reinforcement. However, DBA/2J mice learned slower than C57BL/6J mice when aversive reinforcement was used. In contrast, the two strains performed equally well when appetitive reinforcement was used. The superior performance in C57BL/6J mice in the aversive version of the mBM test was accompanied by a more frequent use of the spatial strategy. In the appetitive version of the mBM test, both strains used the spatial strategy to a similar extent. The present results demonstrate that the cognitive performance of mice depends heavily on motivational factors. Our findings underscore the importance of an effective experimental design when assessing spatial memory and challenges interpretations of impaired hippocampal function in DBA/2J mice drawn on the basis of behavior tests depending on aversive reinforcement. © 2011 Elsevier B.V.