title: Interleukin-1 signaling in the basolateral amygdala is necessary for heroin-conditioned immunosuppression.
abstract: Heroin administration suppresses the production of inducible nitric oxide (NO), as indicated by changes in splenic inducible nitric oxide synthase (iNOS) and plasma nitrate/nitrite. Since NO is a measure of host defense against infection and disease, this provides evidence that heroin can increase susceptibility to pathogens by directly interacting with the immune system. Previous research in our laboratory has demonstrated that these immunosuppressive effects of heroin can also be conditioned to environmental stimuli by repeatedly pairing heroin administration with a unique environmental context. Re-exposure to a previously drug-paired context elicits immunosuppressive effects similar to heroin administration alone. In addition, our laboratory has reported that the basolateral amygdala (BLA) and medial nucleus accumbens shell (mNAcS) are critical neural substrates that mediate this conditioned effect. However, our understanding of the contributing mechanisms within these brain regions is limited. It is known that the cytokine interleukin-1 (IL-1) plays an important role in learning and memory. In fact, our laboratory has demonstrated that inhibition of IL-1β expression in the dorsal hippocampus (DH) prior to re-exposure to a heroin-paired context prevents the suppression of measures of NO production. Therefore, the present studies sought to further investigate the role of IL-1 in heroin-conditioned immunosuppression. Blockade of IL-1 signaling in the BLA, but not in the caudate putamen or mNAcS, using IL-1 receptor antagonist (IL-1Ra) attenuated heroin-conditioned immunosuppression of NO production as measured by plasma nitrate/nitrite and iNOS mRNA expression in spleen tissue. Taken together, these findings suggest that IL-1 signaling in the BLA is necessary for the expression of heroin-conditioned immunosuppression of NO production and may be a target for interventions that normalize immune function in heroin users and patient populations exposed to opiate regimens.
authors.affiliation: University of North Carolina at Chapel Hill, Department of Psychology and Neuroscience, Chapel Hill, NC, 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, Chapel Hill, NC, 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, Chapel Hill, NC, USA.
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Jones
authors.affiliation: Washington State University, College of Veterinary Medicine, Department of Integrative Physiology and Neuroscience, Pullman, WA, 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, Chapel Hill, NC, USA. Electronic address: dlysle@email.unc.edu.
authors.forename: Donald T
authors.initials: DT
authors.lastname: Lysle
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000187:drug effects; D003932:Heroin / Q000494:pharmacology*; D007165:Immunosuppression Therapy; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D008297:Male; D009294:Narcotics / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D009294:Narcotics; D017472:Receptors, Interleukin-1; D003932:Heroin
keywords: Basolateral amygdala; Heroin; IL-1; IL-1 receptor antagonist; Immune conditioning, opioid; Learning; Nitric oxide