Caillé Stéphanie, Espejo Emilio F, Koob George F, Stinus Luis
Lab. de Neuropsychobiologie des Désadaptations, CNRS-UMR 5541, BP31, Université de Bordeaux II, Bordeaux, France.
Pharmacol Biochem Behav. 2002 Jul;72(4):979-86. doi: 10.1016/s0091-3057(02)00810-9.
Previous pharmacological studies have implicated serotonergic brain systems in opiate withdrawal. To test the hypothesis that serotonin (5-HT) has a critical role in the development of opiate withdrawal, we have employed a near-total brain 5-HT system lesion technique (90% depletion) using 5,7-dihydroxytryptamine combined with induction of opiate dependence by implantation of morphine pellets or by repeated injections of increasing doses of morphine. The effects of serotonergic neuron lesion were examined on spontaneous opiate withdrawal (changes in circadian locomotor activity) and naloxone-precipitated opiate withdrawal syndrome (the somatic aspect). The antiwithdrawal properties of clonidine, an alpha(2)-adrenoceptor agonist currently used for clinical treatment for the somatic signs of opiate withdrawal, were tested also in the lesioned rats. Our findings show that serotonergic lesions in morphine-dependent rats did not alter either the spontaneous or the naloxone-induced withdrawal syndrome (with exception of jumping behavior). Moreover, clonidine alleviated the naloxone-induced withdrawal syndrome in lesioned as well as in sham-operated morphine-dependent rats. These results demonstrate that 5-HT systems are not directly responsible for the development of the somatic opiate withdrawal syndrome in morphine-dependent rats.
以往的药理学研究表明，血清素能脑系统与阿片类药物戒断有关。为了验证血清素（5-羟色胺，5-HT）在阿片类药物戒断发展过程中起关键作用这一假设，我们采用了一种近乎全脑的5-HT系统损伤技术（耗竭90%），即使用5,7-二羟基色胺，并通过植入吗啡丸或反复注射递增剂量的吗啡来诱导阿片类药物依赖。研究了血清素能神经元损伤对自发阿片类药物戒断（昼夜运动活动变化）和纳洛酮诱发的阿片类药物戒断综合征（躯体方面）的影响。还在损伤大鼠中测试了可乐定（一种目前用于临床治疗阿片类药物戒断躯体症状的α₂肾上腺素能受体激动剂）的抗戒断特性。我们的研究结果表明，吗啡依赖大鼠中的血清素能损伤既未改变自发戒断综合征，也未改变纳洛酮诱发的戒断综合征（跳跃行为除外）。此外，可乐定减轻了损伤及假手术吗啡依赖大鼠中纳洛酮诱发的戒断综合征。这些结果表明，5-HT系统并非吗啡依赖大鼠躯体阿片类药物戒断综合征发展的直接原因。
