Gabriel S M, Simpkins J W, Millard W J
Brain Res. 1985 Oct 28;346(1):15-21. doi: 10.1016/0006-8993(85)91089-3.
Studies were undertaken to evaluate the acute responses of hypothalamic noradrenergic and dopaminergic neurons and anterior pituitary hormones to naloxone (NAL)-precipitated morphine (MOR) withdrawal in the rat. Ovariectomized female rats were rendered MOR-dependent and injected with NAL (1 mg/kg b.w., s.c.). During precipitated MOR withdrawal, a decline in norepinephrine (NE) concentrations was preceded by an increase in the level of its metabolite normetanephrine (NME) in the medial basal hypothalamus (MBH) as well as the preoptic area-anterior hypothalamus (POA-AH). Both dopamine (DA) and its major acid metabolite, dihydroxyphenylacetic acid (DOPAC), showed increased concentrations in these two hypothalamic regions within 30 min of NAL administration. Elevated luteinizing hormone (LH) and beta-endorphin secretion was evident within 5 min of NAL injection to MOR-dependent rats, while serum prolactin (PRL) increased 15 min into MOR withdrawal. Both growth hormone (GH) and thyroid-stimulating hormone (TSH) were depressed over the course of MOR withdrawal. Although a cause and effect relationship cannot be established, during NAL-precipitated MOR withdrawal, a heightened hypothalamic monoaminergic neuronal activity is accompanied by a differential response of anterior pituitary hormones. The observed responses, which are similar to those seen during acute stress, indicate that MOR withdrawal may activate the same mechanisms which mediate the neuroendocrine response to stress.
开展了多项研究，以评估大鼠下丘脑去甲肾上腺素能和多巴胺能神经元以及垂体前叶激素对纳洛酮（NAL）诱发的吗啡（MOR）戒断的急性反应。将去卵巢的雌性大鼠制成吗啡依赖模型，并注射纳洛酮（1毫克/千克体重，皮下注射）。在诱发吗啡戒断期间，内侧基底下丘脑（MBH）以及视前区-下丘脑前部（POA-AH）中去甲肾上腺素（NE）浓度下降之前，其代谢产物去甲变肾上腺素（NME）水平会升高。多巴胺（DA）及其主要酸性代谢产物二羟基苯乙酸（DOPAC）在注射纳洛酮后30分钟内，在这两个下丘脑区域的浓度均升高。向吗啡依赖大鼠注射纳洛酮后5分钟内，促黄体生成素（LH）和β-内啡肽分泌明显增加，而血清催乳素（PRL）在吗啡戒断15分钟时升高。在吗啡戒断过程中，生长激素（GH）和促甲状腺激素（TSH）均降低。尽管无法确定因果关系，但在纳洛酮诱发的吗啡戒断期间，下丘脑单胺能神经元活动增强，同时垂体前叶激素出现不同反应。观察到的这些反应与急性应激时的反应相似，表明吗啡戒断可能激活了介导对应激的神经内分泌反应的相同机制。
