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The effects of the 5-HT(1A) receptor agonist flesinoxan on passive avoidance in mice were compared with those of the benzodiazepine receptor agonist diazepam. In preliminary experiments, the retention latency to enter a dark compartment in mice subjected to single-training sessions with 0.6-mA electric foot shocks for 4, 8, or 16 s slightly increased in all of the test sessions (immediately, 24 h, and 1 week after the training sessions), but none of these changes were significant. In contrast, mice subjected to double-training sessions with 0.6-mA electric foot shocks for 16 s showed a significant increase in retention latency in all of the test sessions. Pretreatment with either flesinoxan or diazepam 30 min before the double-training sessions with 0.6-mA electric foot shocks for 16 s significantly decreased the retention latency in test sessions 24 h and 1 week later. In contrast, mice pretreated with flesinoxan 24 h before the single-training sessions with 0.6-mA electric foot shocks for 4, 8, or 16 s showed a significant increase in retention latency in the test sessions 24 h and/or 1 week later. Similar enhancements of retention latency in the test sessions 24 h and/or 1 week later were observed also in mice pretreated with flesinoxan 24 h before the double-training sessions. However, in this time interval following injection, pretreatment with diazepam did not affect the retention latency of mice in any of the test sessions. Neither flesinoxan nor diazepam, at the same doses and time intervals used in the passive avoidance study, modified the thresholds for flinching and jumping elicited by electrical stimuli. These results suggest that the activation of 5-HT(1A) receptors, but not benzodiazepine receptors, has a dual effect on the formation of learning and memory for an aversive event that depends on the time interval following receptor activation.

Modulation of Passive Avoidance in Mice by the 5-HT1A Receptor Agonist Flesinoxan: Comparison with the Benzodiazepine Receptor Agonist Diazepam