The use-dependent, nicotinic antagonist BTMPS reduces the adverse consequences of morphine self-administration in rats in an abstinence model of drug seeking.
The use-dependent, nicotinic antagonist BTMPS reduces the adverse consequences of morphine self-administration in rats in an abstinence model of drug seeking.
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DOI：
10.1016/j.neuropharm.2011.05.026
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发表时间：
2011-09
影响因子：
4.7
通讯作者：
Buccafusco JJ
中科院分区：
文献类型：
--
作者：
Hall BJ;Pearson LS;Terry AV Jr;Buccafusco JJ
在这项研究中，使用依赖性，烟碱受体拮抗剂双（2，2，6，6-四甲基-4-哌啶基）癸二酸酯（BTMPS）的能力，以减轻与吗啡在大鼠的不良后果，在所有三个阶段的戒毒模型的药物寻求：自我管理，急性戒断，延迟测试的药物寻求。允许大鼠在操作室内以24小时为基础以主动反应杆自我施用吗啡（FR 1时间表），持续14天。随后评价每只大鼠与自发吗啡戒断相关的刻板行为。然后将大鼠置于标准饲养笼中，持续6周的吗啡长期戒断期。在这段时间后，将每只大鼠放回其各自的操作室中，进行14天的无回报药物寻求反应评估。在三组独立的实验中，在所有三个临床相关阶段向动物施用BTMPS。当与媒介物处理的对照动物相比时，在自我施用阶段期间BTMPS处理导致对吗啡的杠杆反应降低高达34%，以及自我施用的吗啡剂量降低32%。当在自我给药和急性戒断期间给予时，与对照动物相比，BTMPS治疗减少了吗啡使用的急性戒断症状（高达64%），并减少了（高达45%）延长戒断6周后的药物寻求反应。戒断吗啡六周后，BTMPS治疗没有效果。这些结果提供了深入了解中枢胆碱能受体在药物成瘾的发生和维持中的作用。
In this study, the use-dependent, nicotinic receptor antagonist bis (2, 2, 6, 6-tetramethyl-4-piperidinyl) sebacate (BTMPS) was evaluated for its ability to attenuate the adverse consequences associated with morphine in rats in all three phases of an abstinence model of drug seeking: self-administration, acute withdrawal, and delayed test of drug seeking. Rats were allowed to self-administer morphine (FR1 schedule) with an active response lever, on a 24hr basis inside operant chambers, for 14 days. Each rat was subsequently evaluated for stereotypical behaviors associated with spontaneous morphine withdrawal. Rats were then placed in standard housing cages for a six week period of protracted abstinence from morphine. After this period, each rat was placed back into its respective operant chamber for a 14 day assessment of unrewarded drug seeking responses. BTMPS was administered to the animals in all three clinically relevant phases in three separate sets of experiments. BTMPS treatment during the self-administration phase resulted in up to a 34% reduction of lever responses to morphine when compared to vehicle treated control animals, as well as a 32% reduction in the dose of morphine self-administered. When given during self-administration and acute withdrawal, BTMPS treatment decreased acute withdrawal symptoms (up to 64%) of morphine use and reduced (up to 45%) drug seeking responses after six weeks of protracted withdrawal compared to control animals. BTMPS treatment after six weeks of abstinence from morphine had no effect. These results offer insight into the role of central cholinergic receptors in the onset and maintenance of drug addiction.