Fear conditioning in C57/BL/6 and DBA/2 mice: variability in nucleus accumbens function according to the strain predisposition to show contextual- or cue-based responding.

The contribution of the nucleus accumbens shell, the dorsal hippocampus, and the basolateral amygdala to contextual and explicit cue fear conditioning was assessed in C57BL/6 (C57) and DBA/2 (DBA) mice showing differences in processing contextual information associated with consistent but non-pathological variations in hippocampal functionality. Mice from both strains with bilateral ibotenic acid or sham lesions located in each area were introduced in a conditioning chamber and exposed twice to the pairing of a tone (2 x 8 s, 2000 Hz, 80 dB) with a shock (2 s, 0.7 mA). On the following day, mice were first exposed to the training context then to the tone in a different context. Freezing behaviour was scored in all situations. C57 showed more freezing to the context than to the tone whereas DBA showed more freezing to the tone than to the context. In C57, both nucleus accumbens and hippocampal lesions impaired acquisition of contextual fear conditioning but paradoxically improved acquisition of cue fear conditioning, whereas amygdala lesions disrupted performance in every task. In DBA, nucleus accumbens lesions, like amygdala lesions, impaired acquisition of both contextual and cue fear conditioning, whereas hippocampal lesions did not produce any effect. The parallelism between the effect of nucleus accumbens and hippocampus lesions in C57, and between the effect of nucleus accumbens and amygdala lesions in DBA points to a variability in nucleus accumbens function according to the strain specialization to develop context- or cue-based responding.