Diazepam increases the number of punished responses in a conflict-operant paradigm during late proestrus and estrus in the Wistar rat.

Both anxiety-like behavior and the response to anxiolytic drugs vary according to the estrus cycle in the rat. Consequently, anxiety-like behavior and the sensitivity to anxiolytic drugs may be related to hormone level fluctuations occurring during the estrus cycle. In male rats tested in a conflict-operant paradigm, anxiolytic drugs increase immediate punished responding. However, it is unknown whether estrus phases impinge on the immediate punished responses in a conflict-operant paradigm. Therefore, in this study female rats were trained in a conflict-operant paradigm; after training all animals received vehicle or diazepam. Then the number of immediate punished reinforcers was evaluated during the estrus cycle. Results showed that vehicle-treated rats evaluated during late proestrus and estrus obtained a higher (p < 0.05) number of immediate punished reinforcers than rats evaluated during metestrus and diestrus. A low dose of diazepam (1.3 mg/kg; i.p) significantly increased (p < 0.05) the immediate punished responses only in late proestrus and estrus. The highest dose of diazepam tested (2.0 mg/kg; i.p.) significantly increased (p < 0.05) the immediate punished reinforcement in any estrus phase. These results suggest that a lower level of anxiety-like and an increased sensitivity to an anxiolytic drug occurred only in late proestrus and estrus in rats tested in a conflict-operant paradigm.