Javelle N, Renaud B, Lambás-Señas L
Laboratoire de Neuropharmacologie et Neurochimie, INSERM CJF 95-06, Faculté de Pharmacie, Université Claude Bernard, Lyon, France.
J Neurochem. 1997 Feb;68(2):683-90. doi: 10.1046/j.1471-4159.1997.68020683.x.
Using microdialysis, changes in monoamine metabolism were monitored in the locus coeruleus of freely moving rats during opiate withdrawal concomitantly with behavioral symptoms. Rats were infused with morphine (2 mg/kg/h, s.c.) or saline for 5 days and challenged with naltrexone (100 mg/kg, s.c.) on day 6. Following naltrexone challenge, the classic behavioral symptoms of morphine withdrawal were observed in rats treated with morphine but not in saline-infused rats. In morphine-dependent rats, naltrexone induced a marked increase (280%) in dialysate concentrations of 3,4-dihydroxyphenylacetic acid, an index of the functional activity of the noradrenergic neurons in the locus coeruleus. The local concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were also increased (70%) during morphine withdrawal. Taken together, these results (a) confirm in unanesthetized rats the hypothesis of an activation by opiate withdrawal of noradrenergic neurons in the locus coeruleus and (b) suggest an increase in serotonergic transmission in the same nucleus during morphine withdrawal.
利用微透析技术，在阿片类药物戒断期间，对自由活动大鼠蓝斑中的单胺代谢变化进行监测，并同时观察行为症状。大鼠连续5天皮下注射吗啡（2毫克/千克/小时）或生理盐水，在第6天用纳曲酮（100毫克/千克，皮下注射）进行激发试验。纳曲酮激发试验后，吗啡处理的大鼠出现了典型的吗啡戒断行为症状，而生理盐水注射的大鼠未出现。在吗啡依赖的大鼠中，纳曲酮使3,4-二羟基苯乙酸的透析液浓度显著增加（280%），3,4-二羟基苯乙酸是蓝斑中去甲肾上腺素能神经元功能活性的指标。在吗啡戒断期间，血清素代谢产物5-羟基吲哚乙酸的局部浓度也增加了（70%）。综上所述，这些结果（a）在未麻醉的大鼠中证实了阿片类药物戒断激活蓝斑中去甲肾上腺素能神经元的假说，（b）表明在吗啡戒断期间同一核团中血清素能传递增加。
