• Vedrana Bali, Sarah C Simmons, Claire E Manning, Marie A Doyle, Minerva Rodriguez, Ali R Stark, Shantée N Ayala Rosario, A J Robison, and Michelle S Mazei-Robison.
• Dept of Physiology, Michigan State University, East Lansing, MI 48824, United States; Neuroscience Program, Michigan State University, East Lansing, MI 48824, United States.
• Neuroscience. 2021 May 1; 461: 11-22.

AbstractDespite the high prevalence of major depressive disorder (MDD), understanding of the biological underpinnings remains limited. Rodent models suggest that changes in activity and output of dopamine (DA) neurons in the ventral tegmental area (VTA) are important for depressive-like phenotypes. Additionally, brain inflammatory processes are thought to contribute to MDD pathology and inflammation in the VTA has been linked to changes in VTA DA neuronal activity. Thus, we sought to determine whether there is increased inflammatory signaling in the VTA following forms of chronic stress that induce depressive-like symptoms. First, we subjected male mice to either physical or vicarious chronic social defeat stress (CSDS), paradigms known to induce long-term depressive-like behavior and changes in VTA signaling. Second, we subjected male and female mice to subchronic variable stress (SCVS), a paradigm that induces depressive-like behavior only in female mice. We then isolated mRNA from the VTA and assessed proinflammatory gene regulation via RT-PCR. Our results show that physical, but not vicarious, CSDS increases interleukin 1β (IL-1β) mRNA expression and this inversely correlates with social interaction score. In contrast, IL-1β expression was unchanged in male or female mice following SCVS. No significant increases in VTA ionized calcium binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) immunochemistry were detected following CSDS that would be indicative of a robust inflammatory response. In conclusion, we show that chronic stressors distinctively alter expression of proinflammatory genes in the VTA and changes may depend on the severity and time-course of the stress exposure.Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.

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