Cytokine mediation of experimental heart failure-induced anhedonia.
Immune system dysfunction is hypothesized to influence several disease states, including cardiovascular disease and psychological depression. The comorbidity of depression and coronary artery disease may be influenced by immune system-brain interactions involving proinflammatory cytokines. The present studies evaluated an index of depression in a rodent model of heart failure by measuring responses to rewarding electrical brain stimulation, which provides an experimental procedure to operationally define anhedonia in rats. Heart failure led to a rightward shift in the current-response relationship in the brain stimulation paradigm, indicative of reduced rewarding properties of the brain stimulation (i.e., anhedonia). Acute treatment with a tumor necrosis factor antagonist, etanercept, reduced circulating tumor necrosis factor- levels in rats with heart failure and restored responding for electrical brain stimulation. The current findings have implications for the study of pathophysiological mechanisms underlying the association of cardiovascular disease and depression.
Grippo
Angela J
AJ
Department of Psychology, The University of Iowa, Iowa City, Iowa 52242, USA.
Francis
Joseph
J
Weiss
Robert M
RM
Felder
Robert B
RB
Johnson
Alan Kim
AK
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000503:physiopathology; D003863:Depression / Q000209:etiology* / Q000503:physiopathology*; D004558:Electric Stimulation; D000068800:Etanercept; D006333:Heart Failure / Q000523:psychology*; D007074:Immunoglobulin G / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor; D012201:Reward; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept