D-cycloserine selectively decreases nicotine self-administration in rats with low baseline levels of response.
D-cycloserine selectively decreases nicotine self-administration in rats with low baseline levels of response.
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DOI：
10.1016/j.pbb.2010.12.023
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发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
Rose JE
中科院分区：
文献类型：
--
作者：
Levin ED;Slade S;Wells C;Petro A;Rose JE
扩大可用于帮助戒烟的治疗方法的种类将允许针对特定类型的吸烟者定制治疗。关键是要了解哪些吸烟者亚群得到了适当的治疗。本研究使用成年雌性Sprague-Dawley大鼠评价D-环丝氨酸（一种部分NMDA谷氨酸受体激动剂）在减少尼古丁自我给药方面的疗效。训练大鼠通过操作性杠杆反应（FR 1）和辅助视觉刺激器自我给予尼古丁（0.03 mg/kg/输注，IV）。进行了两项D-环丝氨酸对尼古丁自我给药影响的研究：一项急性剂量效应研究（0、10、20和40 mg/kg，sc）和一项慢性研究，在每次试验前给予40 mg/kg，持续两周。评估了对尼古丁自我给药前基线水平低或高的大鼠的影响。在急性研究中，D-环丝氨酸x尼古丁自我给药基线水平存在显著的相互作用。在低基线组中，10 mg/kg D-环丝氨酸显著降低了尼古丁自我给药。在高基线组中，40 mg/kg显著增加了尼古丁自我给药。在重复注射研究中，D-环丝氨酸x尼古丁自我给药基线水平也存在显著的相互作用。慢性D-环丝氨酸显着减少尼古丁自我管理选择性低基线尼古丁使用的大鼠，但与基线尼古丁自我管理水平较高的大鼠无效。NMDA谷氨酸治疗可能特别有助于帮助轻度吸烟者成功戒烟，这突出了对不同类型吸烟者进行不同治疗的必要性。
Expanding the variety of treatments available to aid smoking cessation will allow the treatments to be customized to particular types of smoker. The key is to understand which subpopulations of smokers with the appropriate treatment. This study used adult female Sprague-Dawley rats to evaluate the efficacy of D-cycloserine, a partial NMDA glutamate receptor agonist, in reducing nicotine self-administration. Rats were trained to self-administer nicotine (0.03 mg/kg/infusion, IV) via operant lever response (FR1) with a secondary visual reinforcer. Two studies of D-cycloserine effects on nicotine self-administration were conducted: an acute dose-effect study (0, 10, 20 and 40 mg/kg, sc) and a chronic study with 40 mg/kg given before each test session for two weeks. Effects on rats with low or high pretreatment baseline levels of nicotine self-administration were assessed. In the acute study there was a significant interaction of D-cycloserine x baseline level of nicotine self-administration. In the low baseline group, 10 mg/kg D-cycloserine significantly decreased nicotine self-administration. In the high baseline group, 40 mg/kg significantly increased nicotine self-administration. In the repeated injection study, there was also a significant interaction of D-cyloserine x baseline level of nicotine self-administration. Chronic D-cycloserine significantly reduced nicotine self-administration selectively in rats with low baseline nicotine use, but was ineffective with the rats with higher levels of baseline nicotine self-administration. NMDA glutamate treatments may be particularly useful in helping lighter smokers successfully quit smoking, highlighting the need for diverse treatments for different types of smokers.