Conditioned effects of heroin on proinflammatory mediators require the basolateral amygdala.
Heroin administration alters the induction of nitric oxide, a molecule known to play a critical role in immune function. Previous research has shown that these alterations can be conditioned to environmental stimuli that have been associated with drug administration. Little is known about the brain areas that mediate these effects; however, the basolateral amygdala (BLA) has been implicated in the formation of stimulus-reward associations within models of drug abuse. The present study sought to determine whether inactivation of the BLA would alter heroin's conditioned effects on the expression of inducible nitric oxide synthase (iNOS) and the proinflammatory cytokines TNF-alpha and IL-1beta in the rat. The conditioning procedure involved repeated pairing of heroin with placement into a standard conditioning chamber. To test the conditioned response, animals were returned to the previously drug-paired environment 6 days after the final conditioning session. Prior to testing, animals received intra-BLA microinfusions of a mixture of the GABA agonists muscimol and baclofen. Following removal from the chambers on test day, all animals received subcutaneous lipopolysaccharide to induce systemic expression of iNOS, TNF-alpha and IL-1beta. Analyses using real-time RT-PCR indicated that inactivation of the BLA blocked the suppressive effect of heroin-associated environmental stimuli on iNOS induction and on the expression of the proinflammatory cytokines TNF-alpha and IL-1beta in spleen and liver tissue. This study is important because it is the first to demonstrate that heroin's conditioned effects on proinflammatory mediators require the BLA. These findings may have significant implications for the treatment of heroin users.
Szczytkowski
Jennifer L
JL
Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Lysle
Donald T
DT
D000679:Amygdala / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004660:Encephalitis / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology; D018755:GABA Agonists / Q000494:pharmacology; D003932:Heroin / Q000494:pharmacology*; D006556:Heroin Dependence / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000819:agonists* / Q000276:immunology; D053583:Interleukin-1beta / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000276:immunology; D008297:Male; D009294:Narcotics / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics / Q000276:immunology
D018755:GABA Agonists; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009294:Narcotics; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D003932:Heroin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat