title: Acquisition of heroin conditioned immunosuppression requires IL-1 signaling in the dorsal hippocampus.
abstract: Opioid users experience increased incidence of infection, which may be partially attributable to both direct opiate-immune interactions and conditioned immune responses. Previous studies have investigated the neural circuitry governing opioid conditioned immune responses, but work remains to elucidate the mechanisms mediating this effect. Our laboratory has previously shown that hippocampal IL-1 signaling, specifically, is required for the expression of heroin conditioned immunosuppression following learning. The current studies were designed to further characterize the role of hippocampal IL-1 in this phenomenon by manipulating IL-1 during learning. Experiment 1 tested whether hippocampal IL-1 is also required for the acquisition of heroin conditioned immunosuppression, while Experiment 2 tested whether hippocampal IL-1 is required for the expression of unconditioned heroin immunosuppression. We found that blocking IL-1 signaling in the dorsal hippocampus with IL-1RA during each conditioning session, but not on interspersed non-conditioning days, significantly attenuated the acquisition of heroin conditioned immunosuppression. Strikingly, we found that the same IL-1RA treatment did not alter unconditioned immunosuppression to a single dose of heroin. Thus, IL-1 signaling is not a critical component of the response to heroin but rather may play a role in the formation of the association between heroin and the context. Collectively, these studies suggest that IL-1 signaling, in addition to being involved in the expression of a heroin conditioned immune response, is also involved in the acquisition of this effect. Importantly, this effect is likely not due to blocking the response to the unconditioned stimulus since IL-1RA did not affect heroin's immunosuppressive effects.
authors.affiliation: University of North Carolina at Chapel Hill, Department of Psychology and Neuroscience, CB#3270, Chapel Hill, NC 27599-3270, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Lebonville
authors.affiliation: University of North Carolina at Chapel Hill, Department of Psychology and Neuroscience, CB#3270, Chapel Hill, NC 27599-3270, USA.
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Jones
authors.affiliation: University of North Carolina at Chapel Hill, Department of Psychology and Neuroscience, CB#3270, Chapel Hill, NC 27599-3270, USA.
authors.forename: Lee W
authors.initials: LW
authors.lastname: Hutson
authors.affiliation: University of North Carolina at Chapel Hill, Department of Psychology and Neuroscience, CB#3270, Chapel Hill, NC 27599-3270, USA.
authors.forename: Letty B
authors.initials: LB
authors.lastname: Cooper
authors.affiliation: Washington State University College of Veterinary Medicine, Department of Integrative Physiology and Neuroscience, PO Box 647620, Pullman, WA 99164-7620, USA.
authors.forename: Rita A
authors.initials: RA
authors.lastname: Fuchs
authors.affiliation: University of North Carolina at Chapel Hill, Department of Psychology and Neuroscience, CB#3270, Chapel Hill, NC 27599-3270, USA. Electronic address: dlysle@email.unc.edu.
authors.forename: Donald T
authors.initials: DT
authors.lastname: Lysle
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D003932:Heroin / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007165:Immunosuppression Therapy; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D009294:Narcotics; D003932:Heroin
keywords: Heroin; Hippocampus; IL-1; IL-1 receptor antagonist; Immune conditioning; Learning; Nitric oxide; Opioid