Background: In females, during each sexual cycle, significant fluctuations occur in the production and secretion of ovarian steroid hormones (estrogen and progesterone in the follicular and secretory phases of the ovary, respectively). At the brain level, changes in the excitability of neural circuits caused by hormonal fluctuations manifest as changes in mood and emotional behaviors, etc. Objective: The present study aims to study learning and memory capabilities during the diestrus (DIE) and proestrus (PRO) phases of the sexual cycle of rats. Materials and Methods: In this experimental study 14 mature femal Wistar rats (200-220 gr, 3-4 months) were randomly divided into PRO and DIE groups (n = 7/each). During the experimental period, all rats were undertaken daily vaginal smear cytology and then entered into the behavioral tests: elevated plus maze (for anxiety assessment), open field (for seeking), shuttle box (for memory evaluation). At the end, the results of each test were statistically analyzed and compared between 2 groups. Results: In the elevated plus maze test, the measured parameters were the percentage of entries into the open arm and the percentage of time spent in the open arms. The results showed that, in compare with PRO group, in DIE group the number of entries into the open arm and the time spent in the open arm were significantly reduced (p < 0.0001). In the open field test the measured parameter was the time spent in the central boxes, in compare to peripheral boxes. The resultsshowed that the seeking behavior was significantly higher in PRO group than the DIE group (p < 0.051). In the shuttle box test, the measured parameter was the delay time for the entry into the dark chamber. The results showed that the latency to enter the dark compartment was significantly (p < 0.05) longer the PRO group than DIE group. Conclusion: It can be concluded that this difference in the above parameters are due to the effects of the fluctuations in sex hormones. It seems that, in compare to PRO group, rats in DIE group were more sensitive to stressfull conditions, less restless and more alert.

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