Little P J, Price R R, Hinton R K, Kuhn C M
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710, USA.
Drug Alcohol Depend. 1996 May;41(1):47-54. doi: 10.1016/0376-8716(96)01236-7.
Despite the existence of a well-defined abstinence syndrome in offspring of opiate-dependent mothers, the mechanisms involved in neonatal abstinence remain unclear. The goal of the present study was to determine the contribution of noradrenergic neurons in the opiate abstinence syndrome in neonatal rats (10 days old). First, the ability of the alpha 2-adrenergic agonist, clonidine to attenuate the symptoms of neonatal opiate abstinence precipitated by naloxone was determined. Secondly, the activity of noradrenergic neurons was determined by measuring postmortem levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the hypothalamus, hippocampus and cortex in opiate-abstinent pups. Neonatal opiate abstinence was characterized by an increased incidence of wall climbing, tremors and mouthing. Acute treatment with morphine and naloxone in chronic saline-treated pups also produced the tremor, albeit less severe than in pups treated chronically with morphine. Clonidine (0.2 mg/kg) attenuated the expression of tremor and mouthing in neonates, but increased wall climbing. Clonidine elicited wall climbing in opiate-naive neonates. Treatment with morphine followed by naltrexone increased MHPG levels in all of the brain areas examined, irrespective of the chronic treatment, but naltrexone treatment elicited a larger increase in MHPG levels in pups treated chronically with morphine. Acute morphine treatment increased MHPG levels only in the hypothalamus. The results of the present study provide behavioral and neurochemical data supporting the hypothesis that noradrenergic hyperactivity plays a role in neonatal opiate abstinence.
尽管阿片类药物依赖母亲的后代存在明确的戒断综合征，但新生儿戒断所涉及的机制仍不清楚。本研究的目的是确定去甲肾上腺素能神经元在新生大鼠（10日龄）阿片类药物戒断综合征中的作用。首先，确定α2-肾上腺素能激动剂可乐定减轻纳洛酮诱发的新生儿阿片类药物戒断症状的能力。其次，通过测量阿片类药物戒断幼崽下丘脑、海马和皮质中死后3-甲氧基-4-羟基苯乙二醇（MHPG）的水平来确定去甲肾上腺素能神经元的活性。新生儿阿片类药物戒断的特征是爬壁、震颤和口部动作的发生率增加。在慢性生理盐水处理的幼崽中急性给予吗啡和纳洛酮也会产生震颤，尽管比慢性给予吗啡的幼崽轻。可乐定（0.2mg/kg）可减轻新生儿震颤和口部动作的表现，但增加了爬壁行为。可乐定在未接触过阿片类药物的新生儿中引发了爬壁行为。无论慢性处理如何，吗啡后接纳曲酮治疗均会增加所有检测脑区的MHPG水平，但纳曲酮治疗在慢性给予吗啡的幼崽中使MHPG水平升高幅度更大。急性吗啡治疗仅在下丘脑中增加了MHPG水平。本研究结果提供了行为和神经化学数据，支持去甲肾上腺素能功能亢进在新生儿阿片类药物戒断中起作用的假说。
