Buller K M, Hamlin A S, Osborne P B
School of Biomedical Sciences, Queensland Brain Institute, University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia.
Neuropharmacology. 2005 Aug;49(2):230-42. doi: 10.1016/j.neuropharm.2005.03.014.
In opiate addicts or patients receiving morphine treatment, it has been reported that the immune system is often compromised. The mechanisms responsible for the adverse effects of opioids on responses to infection are not clear but it is possible that central and/or peripheral opioid receptors may be important. We have utilised an experimental immune challenge model in rats, the systemic administration of the human pro-inflammatory cytokine interleukin-1beta (IL-1beta) to study the effects of selectively blocking peripheral opioid receptors only (using naloxone methiodide) or after blocking both central and peripheral opioid receptors (using naloxone). Pre-treatment with naloxone methiodide decreased (15%) IL-1beta-induced Fos-immunoreactivity (Fos-IR) in medial parvocellular paraventricular nucleus (mPVN) corticotropin-releasing hormone (CRH) neurons but increased responses in the ventrolateral medulla (VLM) C1 (65%) and nucleus tractus solitarius (NTS) A2 (110%) catecholamine cell groups and area postrema (136%). However no effect of blocking peripheral opioid receptors was detected in the central nucleus of the amygdala (CeA) or dorsal bed nucleus of the stria terminalis (BNST). We next determined the effect of blocking both central and peripheral opioid receptors with naloxone and, when compared to the naloxone methiodide pre-treated group, a further 60% decrease in Fos-IR mPVN CRH neurons induced by IL-1beta was detected, which was attributed to block of central opioid receptors. Similar comparisons also detected decreases in Fos-IR neurons induced by IL-1beta in the VLM A1, VLM C1 and NTS A2 catecholamine cell groups, area postrema, and parabrachial nucleus. In contrast, pre-treatment with naloxone increased Fos-IR neurons in CeA (98%) and dorsal BNST (72%). These results provide novel evidence that endogenous opioids can influence central neural responses to systemic IL-1beta and also suggest that the differential patterns of activation may arise because of actions at central and/or peripheral opioid receptors that might be important in regulating behavioural, hypothalamic-pituitary-adrenal axis and sympathetic nervous system responses during an immune challenge.
据报道，在阿片类药物成瘾者或接受吗啡治疗的患者中，免疫系统常常受到损害。阿片类药物对感染反应产生不良反应的机制尚不清楚，但中枢和/或外周阿片受体可能起重要作用。我们利用大鼠实验性免疫应激模型，通过全身注射人促炎细胞因子白细胞介素-1β（IL-1β），研究仅选择性阻断外周阿片受体（使用甲基碘化纳洛酮）或同时阻断中枢和外周阿片受体（使用纳洛酮）后的效果。甲基碘化纳洛酮预处理使内侧小细胞室旁核（mPVN）促肾上腺皮质激素释放激素（CRH）神经元中IL-1β诱导的Fos免疫反应性（Fos-IR）降低了15%，但使腹外侧延髓（VLM）C1（65%）、孤束核（NTS）A2（110%）儿茶酚胺细胞群和最后区（136%）的反应增加。然而，在杏仁核中央核（CeA）或终纹床核背侧（BNST）未检测到阻断外周阿片受体的作用。接下来，我们确定了用纳洛酮同时阻断中枢和外周阿片受体的效果，与甲基碘化纳洛酮预处理组相比，检测到IL-1β诱导的mPVN CRH神经元Fos-IR进一步降低了60%，这归因于中枢阿片受体的阻断。类似的比较还检测到IL-1β诱导的VLM A1、VLM C1和NTS A2儿茶酚胺细胞群、最后区和臂旁核中Fos-IR神经元减少。相反，纳洛酮预处理使CeA（98%）和BNST背侧（72%）的Fos-IR神经元增加。这些结果提供了新的证据，表明内源性阿片类物质可影响中枢对全身IL-1β的神经反应，也表明激活模式的差异可能是由于中枢和/或外周阿片受体的作用引起的，这些受体在免疫应激期间调节行为、下丘脑-垂体-肾上腺轴和交感神经系统反应中可能很重要。
