Effects of dominance status on conditioned defeat and expression of 5-HT1A and 5-HT2A receptors

Abstract

Past experience can alter how individuals respond to stressful events. The brain serotonin system is a key factor modulating stress-related behavior and may contribute to individual variation in coping styles. In this study we investigated whether dominant and subordinate hamsters respond differently to social defeat and whether their behavioral responses are associated with changes in 5-HT1A and 5-HT2A receptor immunoreactivity in several limbic brain regions. We paired weight-matched hamsters in daily aggressive encounters for two weeks so that they formed a stable dominance relationship. We also included controls that were exposed to an empty cage each day for two weeks. Twenty-four hours after the final pairing or empty cage exposure, subjects were socially defeated in 3, 5-min encounters with a more aggressive hamster. Twenty-four hours after social defeat, animals were tested for conditioned defeat in a 5-min social interaction test with a non-aggressive intruder. We collected brains following conditioned defeat testing and performed immunohistochemistry for 5-HT1A and 5-HT2A receptors. We found that dominants showed less submissive and defensive behavior at conditioned defeat testing compared to both subordinates and controls. Additionally, both dominants and subordinates had an increased number of 5-HT1A immunopositive cells in the basolateral amygdala compared to controls. Subordinates also had more 5-HT1A immunopositive cells in the dorsal medial amygdala than did controls. Finally, dominants had fewer 5-HT1A immunopositive cells in the paraventricular nucleus of the hypothalamus compared to controls. Our results indicate that dominant social status results in a blunted conditioned defeat response and a distinct pattern of 5-HT1A receptor expression, which may contribute to resistance to conditioned defeat.

Figure 1

The diagrams indicate the location of brain regions selected for quantification of 5-HT1A and 5-HT2A receptor immunoreactivity. The diagrams were modified from a hamster brain atlas and values indicate the distance from bregma [61]. The box sizes used for quantification are as follows: 330 μm × 439 μm (BLA, CeA, LA, dMeA, vMeA, CA1, and DG); 165 μm × 219 μm (PVN).

Figure 2

Representative photomicrographs of a hamster coronal brain section used for immunohistochemical analyses. a) Photomicrograph of tissue from the BLA labeled for 5-HT1A receptor immunoreactivity. b) Photomicrograph of tissue from the BLA that was labeled for 5-HT2A receptor immunoreactivity.

Figure 3

Agonistic behavior during daily encounters. Encounters were 10 min on Day 1 and 5 min on Days 2-14. a) Duration (mean ± SE) of aggressive behavior displayed by dominants (N = 12) and subordinates (N = 11) during fourteen days of encounters. Dominant animals showed consistent levels of aggression throughout all encounters, while subordinates showed no aggression. b) Duration (mean ± SE) of submissive and defensive behavior displayed by dominants and subordinates throughout the encounters. Subordinate animals showed consistent levels of submissive and defensive behavior, while dominants showed none. c) Number (mean ± SE) of attacks during each daily encounter. Subordinates never attacked, while dominants showed consistent levels of attacking. d) Number (mean ± SE) of flees during each daily encounter. Subordinates showed consistent levels of fleeing, while dominants never fled.

Figure 4

Durations (mean ± SE) of submissive, aggressive, social and nonsocial behaviors are shown during a 5 min test with a non-aggressive intruder. All subjects received social defeat training 24h prior to testing. Dominant (N = 12) and subordinate (N = 11) individuals experienced 14 days of dyadic encounters prior to testing. Empty cage control (N = 12) individuals were exposed to a clean, empty cage daily for 14 days. An asterisk (*) indicates p < 0.05 compared to subordinates and empty cage controls.

Figure 5

Number (mean ± SE) of 5-HT1A receptor immunopositive cells measured in several brain regions following conditioned defeat testing. An asterisk (*) indicates p < 0.05 compared to empty cage controls. Sample sizes ranged from 10-12 individuals per group, because of variation in tissue quality.

Figure 6

Number (mean ± SE) of 5-HT2A receptor immunopositive cells measured in the BLA following conditioned defeat testing. There were no significant differences between the groups. Dominant (N = 12), Subordinate (N = 11), Empty Cage (N = 12).