Proinflammatory signaling regulates voluntary alcohol intake and stress-induced consumption after exposure to social defeat stress in mice.
Proinflammatory activity has been postulated to play a role in addictive processes and stress responses, but the underlying mechanisms remain largely unknown. Here, we examined the role of interleukin 1 (IL-1) and tumor necrosis factor-α (TNF-α) in regulation of voluntary alcohol consumption, alcohol reward and stress-induced drinking. Mice with a deletion of the IL-1 receptor I gene (IL-1RI KO) exhibited modestly decreased alcohol consumption. However, IL-1RI deletion affected neither the rewarding properties of alcohol, measured by conditioned place preference (CPP), nor stress-induced drinking induced by social defeat stress. TNF-α signaling can compensate for phenotypic consequences of IL1-RI deletion. We therefore hypothesized that double deletion of both IL-1RI and TNF-1 receptors (TNF-1R) may reveal the role of these pathways in regulation of alcohol intake. Double KOs consumed significantly less alcohol than control mice over a range of alcohol concentrations. The combined deletion of TNF-1R and IL-1RI did not influence alcohol reward, but did prevent increased alcohol consumption resulting from exposure to repeated bouts of social defeat stress. Taken together, these data indicate that IL-1RI and TNF-1R contribute to regulation of stress-induced, negatively reinforced drinking perhaps through overlapping signaling events downstream of these receptors, while leaving rewarding properties of alcohol largely unaffected.
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Camilla
C
Karlsson
Department of Physiology and Pharmacology, University of Georgia, Athens, GA.
Jesse R
JR
Schank
Laboratory of Clinical and Translational Studies, National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Bethesda, MD, USA.
Faazal
F
Rehman
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Andrea
A
Stojakovic
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Karl
K
Björk
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Estelle
E
Barbier
Laboratory of Clinical and Translational Studies, National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Bethesda, MD, USA.
Matthew
M
Solomon
Laboratory of Clinical and Translational Studies, National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Bethesda, MD, USA.
Jenica
J
Tapocik
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
David
D
Engblom
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Annika
A
Thorsell
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Markus
M
Heilig
D000428:Alcohol Drinking / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001522:Behavior, Animal; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D003214:Conditioning, Classical; D000431:Ethanol / Q000008:administration & dosage; D007249:Inflammation; D007375:Interleukin-1 / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012929:Psychological Distance; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000276:immunology*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013315:Stress, Psychological / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D002492:Central Nervous System Depressants; C583355:IL1R1 protein, mouse; D007375:Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol
CPP; IL-1RI; TNF-1R; alcohol; cytokines; social defeat stress