Resumo

Goals: In line with the reasoning that emotion modulates declarative memory, a clear relationship between anxiety levels and performance has been extensively demonstrated in rodents submitted to the plus-maze discriminative avoidance task (PDAT - a model of aversive memory that allows concomitant evaluation of anxiety levels) (Silva & Frussa-Filho, J Neurosci Met, 102:117, 2000). However, most of studies were performed in male rodents, and there is growing evidence that the emotional aspects of tasks are in the core of the usually reported sexual dimorphism in memory performance. The goal of this study was to evaluate the effect of estrous cycle on the effects of the anxiolytic diazepam in memory and anxiety-related behaviors in the PDAT. Methods: Female Wistar rats (3 months-old) were used in this study. Estrous cycle was determined by vaginal cytology for at least 10 days before training and only rats with two regular cycles were used. Groups of females in estrus, proestrus or metestrus/diestrus were treated i.p. with saline or 2.0mg/kg diazepam. After 30 min, rats were submitted to the training session of PDAT, performed in a modified plus-maze with two opens arms, one aversive arm (AV - light and noise while upon entrance of the animal) and one non-aversive arm (NAV). Twenty-four hours later they were tested in the same apparatus without any injection or aversive stimuli. Memory was evaluated by the comparison of the time spent in aversive vs. non-aversive enclosed arms and anxiety was evaluated by time spent in open arms. Results: Training session: all groups spent significant more time (seconds) in NAV compared to AV, indicating learning of the task (mean ± SE: control metestrus/diestrus = 438.3±69.17 NAV – 30.49±9.82 AV; control proestrus = 466.6±55.98 NAV - 27±11.87 AV; control estrus = 417.7±60.41 NAV – 24.08±3.92 AV; diazepam 2.0mg/kg metestrus/diestrus = 337.6±73.43 NAV – 57.26±12.79 AV; diazepam 2.0mg/kg proestrus = 438.9±104.7 NAV – 15.1±8.7 AV; diazepam 2.0mg/kg estrus = 334.8±64.44 NAV – 48.95±8.07 AV). Test session: time in NAV was significantly increased compared to AV only in control metestrus/diestrus and diazepam 2.0mg/kg proestrus groups (p<0.05). There was a tendency for a difference between NAV and AV (p=0.09) in the control proestrus group (control metestrus/diestrus = 403.14±58 NAV – 100.47±38.7 AV; control proestrus = 409.4±78.7 NAV – 96.4±51.1 AV; control estrus = 330.38±79.06 NAV – 156.9±73.9 AV; diazepam 2.0mg/kg metestrus/diestrus = 264.86±30.41 NAV – 189.7±25.56 AV; diazepam 2.0mg/kg proestrus = 462.08±61.97 NAV – 63.76±30.57 AV; diazepam 2.0mg/kg estrus = 232.51±47.72 NAV – 206.88±43.32 AV). No differences were found in percentage of time in opens arms in training or test sessions. Conclusion: In summary, the results indicated that: (1) the amnestic (but not the anxiolytic) effect of diazepam in PDAT was demonstrated in female rats (at least in the dose used); (2) control female in estrus presented retrieval deficits compared to other phases and (3) rats in proestrus did not showed amnesic effects of diazepam in the PDAT. Together with previous results, our findings suggest that memory-anxiety relationships can be influenced by hormonal states. Further studies will be necessary to clarify the mechanisms related to differences in effects of diazepam on memory and anxiety among several cycle phases and also from previous results reported for male rats.