Evidence for the nucleus accumbens as a neural substrate of heroin-induced immune alterations.
Administration of opioid drugs such as heroin produces several immunosuppressive effects, including decreases in natural killer (NK) cell activity, lymphocyte proliferative responses, and nitric oxide production. Interestingly, opioids have been shown to alter many immune parameters indirectly by modulating the immunoregulatory actions of the central nervous system. Recently, it has been demonstrated that morphine inhibits NK cell activity through a neural pathway that requires the activation of dopamine D(1) receptors in the nucleus accumbens shell. The present study examined whether the nucleus accumbens also mediates the effects of heroin, a more commonly abused opioid, on several parameters of immune status in Lewis rats. The results showed that bilateral administration of the dopamine D(1) receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH-23390; 0.015 and 0.15 microg/side) into the nucleus accumbens shell blocked decreases in splenic NK activity produced by heroin (3 mg/kg s.c.) but did not attenuate the suppression of splenocyte proliferative responses to concanavalin-A or lipopolysaccharide (LPS). A subsequent experiment was performed to evaluate the effect of D(1) receptor antagonism on LPS-induced expression of inducible nitric-oxide synthase (iNOS) in vivo. These results showed that intra-accumbens SCH-23390 administration prevented heroin-induced reductions of iNOS mRNA expression in spleen, liver, and lung tissues and attenuated the suppression of nitric oxide levels in plasma. Collectively, these findings indicate that nucleus accumbens dopamine D(1) receptors are critically involved in heroin-induced immune alterations.
Saurer
Timothy B
TB
Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3270, USA.
Ijames
Stephanie G
SG
Lysle
Donald T
DT
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D003932:Heroin / Q000009:adverse effects / Q000494:pharmacology*; D007107:Immune System / Q000187:drug effects* / Q000276:immunology; D007165:Immunosuppression Therapy; D007694:Killer Cells, Natural / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D001552:Benzazepines; D018492:Dopamine Antagonists; D008070:Lipopolysaccharides; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D003208:Concanavalin A; D009569:Nitric Oxide; D003932:Heroin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat