Chronic stress is associated with a deregulation of the hypothalamus-pituitary adrenal (HPA) axis and can result in behavioral abnormalities, such as depressive behavior. Adrenalectomy (ADX) inhibits the production and release of corticosterone, impairing the response towards stressors, and thus may prevent stress-induced depressive behavior. We aim to determine behavioral and neuroinflammatory effects of HPA-axis disruption via bilateral adrenalectomy (ADX) in animals submitted to repeated...
Materials & Methods
8-weeks old male Wistar rats were divided into four groups: ADX+RSD; ADX+Control; Sham+RSD; Sham+Control. Seven days after ADX surgery, animals were submitted to a 5 days RSD or Control protocols. One- and two days after the last RSD trial, animals went through an open field and social interaction test, respectively. 14 days after RSD, animals went through a 30 minutes [ 11 C]-PBR28 scan for microglia activation. Multifactorial ANOVA was performed for statistical assessment.
There was a significant effect of RSD (p=0.038) and ADX (p=0.049) on the social interaction of the animals, as well as an interaction between surgery and RSD (p=0.042). Post-hoc analysis showed a significantly lower social interaction of Sham+RSD when 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 nor locomotion effect of RSD or ADX (p>0.05). Microglial activation assessed through [ 11...
HPA-axis signaling disruption is able to counterbalance the impairment on the social behavior of these animals. In contrast, no effects of ADX or RSD were observed in other behavioral paradigms. Neuroinflammation was also not observed two weeks after the RSD, suggesting that the inflammatory response of microglial cells is too mild to be detected by PET or that neuroinflammation was only transient and already resolved at the time of measurement.