Suppression of natural killer cell activity by morphine is mediated by the nucleus accumbens shell

Saurer, Timothy B.; Carrigan, Kelly A.; Ijames, Stephanie G.; Lysle, Donald T.

doi:10.1016/j.jneuroim.2005.11.009

Cited by 48 publications

(46 citation statements)

References 37 publications

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“…Alterations in dopamine signaling produced by opioid exposure may be particularly relevant to opioid-induced immune dysfunction given reports that mesoaccumbens dopamine neurons modulate the immune response (Deleplanque et al, 1994;Devoino et al, 1997). Previous work from our laboratory has demonstrated that morphine-induced suppression of NK cell activity is mediated by dopamine D 1 type receptors located in the nucleus accumbens shell, whereas dopamine D 2 type receptors do not seem to be involved (Saurer et al, 2006a). The present study supports and extends our previous work by showing that D 1 receptors in the nucleus accumbens shell also mediate the inhibitory effects of heroin on splenic NK activity and LPS-induced nitric oxide production.…”

Section: Discussionmentioning

confidence: 93%

“…For this manipulation, animals were assigned to one of six groups (n ϭ 5-6/group) in which they received a bilateral microinjection of SCH-23390 (0, 0.015, or 0.15 g/side) into the nucleus accumbens shell immediately before injection with saline or heroin (3 mg/kg s.c.). The doses of SCH-23390 used in the current study were selected based on our previous work that showed that morphine-induced suppression of NK activity is partially attenuated at a dose of 0.015 g/side and fully blocked at a dose of 0.15 g/side (Saurer et al, 2006a). In addition, because the goal of the microinjection studies was to determine whether SCH-23390 administration would block the effects of heroin, we selected the 3-mg/kg dose of heroin, because this was the lowest dose that produced the most prominent and consistent effects across all immune parameters examined in the dose-response experiment.…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, at least some of morphine's immunomodulatory effects are also dependent on dopamine transmission. Specifically, the activation of dopamine D 1 receptors in the nucleus accumbens shell is necessary for morphine to suppress splenic NK cell activity and sufficient to inhibit NK responses in the absence of morphine (Saurer et al, 2006a). Thus, nucleus accumbens dopamine receptors seem to play a critical role in neuroimmune modulation by morphine.…”

mentioning

confidence: 99%

“…First, based on our prior investigations indicating the importance of the nucleus accumbens in the immunological effects of morphine (Saurer et al, 2006a), we sought to determine whether the nucleus accumbens was also involved in heroin's suppressive effects on splenic NK activity and mitogen-induced lymphocyte proliferation. Second, to further explore the mechanisms of heroin's effects in the context of an in vivo immune response, the present study assessed the role of nucleus accumbens D 1 receptors in heroin-induced alterations of inducible nitric-oxide synthase (iNOS) expression.…”

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confidence: 99%

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Evidence for the Nucleus Accumbens as a Neural Substrate of Heroin-Induced Immune Alterations

Saurer

Ijames²,

Lysle³

2009

J Pharmacol Exp Ther

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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-(ϩ)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH-23390; 0.015 and 0.15 g/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.Opioid drug use is associated with adverse health consequences. Heroin abusers display abnormalities in basic immune parameters and have high rates of viral, bacterial, and fungal infections (Louria et al., 1967;Govitrapong et al., 1998). Although the high incidence of infectious diseases among abusers is commonly attributed to increased pathogen exposure or insalubrious behaviors, opioids exert potent immunomodulatory effects that may further enhance infection susceptibility. Controlled studies in humans demonstrate that morphine produces immunosuppressive effects in healthy, nondrug-using subjects (Yeager et al., 1995), and clinical reports indicate that higher doses of opioid analgesics are associated with greater frequencies of infectious complications among burn victims and patients that underwent cardiac surgery (El Solh et al., 2006;Schwacha et al., 2006). Thus, the use of opioids, whether for therapeutic or recreational purposes, may directly influence resistance to infectious diseases.In animal models, morphine has been shown to suppress a variety of immune parameters, but the mechanisms underlying these effects are not fully understood Lockwood et al., 1994). Opioids modulate immunity in a highly complex manner by interacting with opioid receptors expressed by multiple cell types throughout the body. For exa...

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Section: Discussionmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Evidence for the Nucleus Accumbens as a Neural Substrate of Heroin-Induced Immune Alterations

Saurer

Ijames²,

Lysle³

2009

J Pharmacol Exp Ther

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“…As a result, substantial systemic opioid-sparing is achieved, which may minimize the immunosuppressive effects from systemic opioids. 9,11 It has been shown that intrathecal morphine does not affect peripheral lymphocyte (NK cells) function. 12,13 This entire concept may have clinical implications for oncological patients undergoing surgery with regional anesthesia.…”

mentioning

confidence: 99%

Perioperative management and oncological outcomes following radical cystectomy for bladder cancer: a matched retrospective cohort study

Weingarten

Taccolini

Ahle

et al. 2016

Can J Anesth/J Can Anesth

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Opioid Analgesics and the Risk of Serious Infections Among Patients With Rheumatoid Arthritis: A Self‐Controlled Case Series Study

Wiese

Griffin

Stein

et al. 2016

Arthritis & Rheumatology

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Objective Animal and in vitro studies suggest that certain opioid analgesics impair crucial immune functions. We sought to determine if opioid use is associated with an increased risk of serious infections in patients with rheumatoid arthritis (RA). Methods We conducted a self-controlled case series analysis on a retrospective cohort of 13,796 patients with RA enrolled in Tennessee Medicaid (1995–2009). We performed within-person comparisons of the risk of hospitalizations for serious infections during periods of opioid use compared with non-use using conditional Poisson regression. Fixed confounders were accounted for by design, and time-varying confounders included age, the use of disease-modifying anti-rheumatic drugs, glucocorticoids and proton-pump inhibitors. Additional analyses examined new opioid use, use of opioids known to have immunosuppressive properties, long acting opioid use, and different opioid dosages. Sensitivity analyses accounted for potential protopathic bias and confounding by indication. Results Among 1,790 patients with RA who had at least one hospitalization for serious infection, the adjusted incidence rate of serious infection was higher during periods of current opioid use compared with non-use [incidence rate ratio (IRR): 1.39 (95% confidence interval (CI): 1.19–1.62)]. The incidence rate was also higher during periods of long-acting opioid use, immunosuppressive opioid use and new opioid use compared with non-use [IRR: 2.01 (95% CI: 1.52–2.66); IRR: 1.72 (95% CI: 1.33–2.23); IRR: 2.38 (95% CI: 1.65–3.42), respectively]. Results of sensitivity analyses were consistent with the main findings. Conclusions In within-person comparisons of patients with RA, opioid use was associated with an increased risk of hospitalizations for serious infection.

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Suppression of natural killer cell activity by morphine is mediated by the nucleus accumbens shell

Cited by 48 publications

References 37 publications

Evidence for the Nucleus Accumbens as a Neural Substrate of Heroin-Induced Immune Alterations

Evidence for the Nucleus Accumbens as a Neural Substrate of Heroin-Induced Immune Alterations

Perioperative management and oncological outcomes following radical cystectomy for bladder cancer: a matched retrospective cohort study

Opioid Analgesics and the Risk of Serious Infections Among Patients With Rheumatoid Arthritis: A Self‐Controlled Case Series Study

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