The protective effects of resveratrol on social stress-induced cytokine release and depressive-like behavior.
Social stress is a risk factor for psychiatric disorders, however only a subset of the population is susceptible while others remain resilient. Inflammation has been linked to the pathogenesis of psychosocial disorders in humans and may underlie these individual differences. Using a resident-intruder paradigm capable of revealing individual differences in coping behavior and inflammatory responses, the present study determined if resveratrol (RSV; 0, 10, 30mg/kg/day) protected against persistent stress-induced inflammation in socially defeated rats. Furthermore, the antidepressant efficacy of RSV was evaluated using the sucrose preference test. Active coping rats were characterized by more time spent in upright postures and increased defeat latencies versus passive coping rats. Five days after defeat, flow cytometry revealed enhanced stimulation of proinflammatory proteins (IL-β, TNF-α) in spleen cells of passive rats as compared to active coping and controls, an effect that was blocked by both doses of RSV. Furthermore, only passive coping rats exhibited increased proinflammatory proteins (IL-1β, TNF-α, GM-CSF) in the locus coeruleus (LC), a noradrenergic brain region implicated in depression. Notably, only 30mg/kg RSV blocked LC neuroinflammation and importantly, was the only dose that blocked anhedonia. Alternatively, while stress had minimal impact on resting cytokines in the dorsal raphe (DR), RSV dose-dependently reduced DR cytokine expression. However, this did not result in changes in indoleamine 2,3-dioxygenase activity or serotonin levels. Taken together, these data suggest that social stress-induced depressive-like behavior evident in passive coping rats may be driven by stress-induced neuroinflammation and highlight natural anti-inflammatory agents to protect against social stress-related consequences.
Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Columbia, SC, USA.
Julie E
JE
Finnell
Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Columbia, SC, USA.
Calliandra M
CM
Lombard
Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Columbia, SC, USA.
Michael N
MN
Melson
Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.
Narendra P
NP
Singh
Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.
Mitzi
M
Nagarkatti
Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.
Prakash
P
Nagarkatti
Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Columbia, SC, USA.
James R
JR
Fadel
Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Columbia, SC, USA.
Christopher S
CS
Wood
Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Columbia, SC, USA. Electronic address: Susan.Wood@uscmed.sc.edu.
Susan K
SK
Wood
D000223:Adaptation, Psychological; D059445:Anhedonia; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D008125:Locus Coeruleus / Q000378:metabolism; D008297:Male; D011903:Raphe Nuclei / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012931:Social Environment; D013154:Spleen / Q000378:metabolism; D013267:Stilbenes / Q000627:therapeutic use*; D013315:Stress, Psychological / Q000188:drug therapy* / Q000523:psychology
D000975:Antioxidants; D016207:Cytokines; D013267:Stilbenes; D000077185:Resveratrol
Coping; Depression; Inflammation; Resveratrol; Social stress