Estrous cycle state-dependent renewal of appetitive behavior recruits unique patterns of mRNA in female rats.

INTRODUCTION

Renewal is a behavioral phenomenon wherein extinction learning fails to generalize between different contextual environments, thereby representing a significant challenge to extinction-based rehabilitative therapies. Previously, we have shown that renewal of extinguished appetitive behavior differs across the estrous cycle of the female rat. In this experiment that effect is replicated and extended upon to understand how the estrous cycle may modulate contextual representation at the neuronal population level to drive renewal.

METHODS

Estrous cycle stage [i.e., proestrus (P, high hormone) or metestrus/diestrus (M/D, low hormone)] was considered during two important learning and behavioral expression windows: at extinction training and during long-term memory (LTM)/renewal testing. Cellular compartment analysis of temporal activity using fluorescence hybridization (catFISH) for mRNA was conducted after the distinct context-stimulus exposures.

RESULTS

Rats in P during context-dependent extinction training but in a different stage of the estrous cycle during LTM and renewal testing (P-different) were shown to exhibit more renewal of conditioned foodcup (but not conditioned orienting) behavior compared to rats in other estrous cycle groups. Importantly, we discovered this depends on the order of tests. P-different rats showed differential mRNA expression in regions of the prefrontal cortex (PFC), amygdala, and hippocampus (HPC). For each case P-different rats had more co-expression (i.e., expression of both nuclear and cytoplasmic) of mRNA compared to other groups; specific to the dorsal HPC, P-different rats also had a more robust mRNA response to the extinction context exposure.

CONCLUSION

These data suggest female rats show estrous cycle state-dependent renewal of appetitive behavior, and differences in context and conditioned stimulus representation at the neuronal level may drive this effect.