Sex differences and estrous cycle changes in hippocampus-dependent fear conditioning

Abstract

Male and naturally cycling female rats were tested in a fear conditioning paradigm that encompassed both hippocampus-dependent and -independent components. The females were both conditioned and tested for retention at the same stage of the estrous cycle, during either estrus or proestrus. Male rats followed a regime similar to that for the female rats. Approximately 2 weeks after conditioning, the animals were examined for retention of the spatial context and of an explicitly paired conditioning tone. All animals showed a similar degree of conditioning to the tone. However, female proestrous rats showed less spatial-contextual conditioning than did male or estrous female rats. These results suggest that the changes found during the proestrous part of the cycle are related to hippocampal information processing and not to general changes in learning ability, to shock sensitivity, or to state-dependent learning. The results are discussed and related to previous findings regarding estrous cycle changes in behavior, anatomy, and physiology.