Social stress-dependent changes on behavior and inflammatory parameters in animals with HPA-axis disruption

Aim/Introduction: Chronic stress is associated with aderegulation of the hypothalamus-pituitary adrenal (HPA)axis and can result in behavioral abnormalities, such asdepressive behavior. Adrenalectomy (ADX) inhibits theproduction and release of corticosterone, impairingthe response towards stressors, and thus may preventstress-induced depressive behavior. We aim to determinebehavioral and neuroinflammatory effects of HPA-axisdisruption via bilateral adrenalectomy (ADX) in animalssubmitted to repeated social defeat (RSD). Materials and Methods: 8-weeks old male Wistar rats were dividedinto four groups: ADX+RSD; ADX+Control; Sham+RSD;Sham+Control. Seven days after ADX surgery, animals weresubmitted to a 5 days RSD or Control protocols. One- andtwo days after the last RSD trial, animals went through anopen field and social interaction test, respectively. 14 daysafter RSD, animals went through a 30 minutes [11C]-PBR28scan for microglia activation. Multifactorial ANOVA wasperformed for statistical assessment. Results: There was asignificant effect of RSD (p=0.038) and ADX (p=0.049) onthe social interaction of the animals, as well as an interactionbetween surgery and RSD (p=0.042). Post-hoc analysisshowed a significantly lower social interaction of Sham+RSDwhen compared with the other groups (vs. Control+ADX,p=0.032; Control+Sham, p=0.023; ADX+RSD, p=0.035).Open field analysis showed no anxiety-like behavior norlocomotion effect of RSD or ADX (p>0.05). Microglialactivation assessed through [11C]-PBR28 also showed noeffect of RSD or ADX (p>0.05). Conclusion: HPA-axis signalingdisruption is able to counterbalance the impairment on thesocial behavior of these animals. In contrast, no effects ofADX or RSD were observed in other behavioral paradigms.Neuroinflammation was also not observed two weeks afterthe RSD, suggesting that the inflammatory response ofmicroglial cells is too mild to be detected by PET or thatneuroinflammation was only transient and already resolvedat the time of measurement. References: None