Effects of 5-HT1A Receptors on the Development of Stress-Induced Changes in Behavior

Social defeat leads to both increased anxiety-like behavior and the formation of a fear memory for a specific opponent. We have shown that serotonin (5-HT) signaling, particularly in the basolateral amygdala (BLA), alters the acquisition of the conditioned defeat response in Syrian hamsters. While activation of 5-HT1A receptors impairs the acquisition of conditioned defeat, it is unclear whether these receptors alter the development of anxiety-like behavior or formation of fear memories. One method for investigating the formation of defeat-induced fear memories is to measure avoidance of former opponents, and many researchers have reliably used the open field as a measure of anxiety in rodents. In this study, we investigated whether activation of 5-HT1A receptors prior to social defeat would reduce subsequent avoidance of a former opponent but not alter anxiety-like behavior. We also investigated whether activation of 5-HT1A receptors prior to social defeat would reduce the expression of Arc immunoreactivity in the BLA. We administered 8-OH-DPAT (0.0, 0.25, 0.5 mg/kg), a 5-HT1A receptor agonist, prior to 3, 5-minute social defeats and 24- hours later exposed hamsters (Mesocricetus auratus) to a social interaction test to measure the conditioned defeat response immediately followed by a Y-maze test to measure avoidance of a former opponent and an open field test to measure anxiety. In a separate experiment, we administered 8-OH-DPAT (0.0, 0.25 mg/kg) prior to 3, 5-minute social defeats and 2- hours later brains were perfused and removed for Arc immunohistochemistry. We found that administration of 8-OH-DPAT prior to social defeat reduced the acquisition of conditioned defeat compared to vehicle controls. We also found that administration of 8-OH-DPAT prior to social defeat reduced subsequent avoidance of former opponents but did not alter the classic measures of anxiety in the open field. 8-OH-DPAT administration prior to defeat also impaired Arc immunoreactivity in the BLA. These results suggest that 5-HT1A receptors modulate the fear memory associated with the social defeat experience. Furthermore, these results raise the possibility that 5-HT1A receptor activation disrupts Arc expression in the BLA and thereby impairs the development of a fear memory that is essential for the conditioned defeat response.