D-cycloserine deters reacquisition of cocaine self-administration by augmenting extinction learning.
D-cycloserine deters reacquisition of cocaine self-administration by augmenting extinction learning.
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DOI：
10.1038/npp.2009.139
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发表时间：
2010-01
影响因子：
7.6
通讯作者：
Kantak, Kathleen M.
中科院分区：
文献类型：
--
作者：
Dhonnchadha, Brid A. Nic;Szalay, Jonathan J.;Achat-Mendes, Cindy;Platt, Donna M.;Otto, Michael W.;Spealman, Roger D.;Kantak, Kathleen M.
加强线索暴露（消退）治疗与认知增强药物治疗可能提供一个有效的策略，打击可卡因复吸。为了在临床前水平上研究这种可能性，训练大鼠和松鼠猴在简短的视觉提示下自我施用可卡因。杠杆按下随后熄灭扣留可卡因注射，同时保持响应的线索。评价了甘氨酸部分激动剂D-环丝氨酸（DCS;大鼠15和30 mg/kg，猴3和10 mg/kg）对可卡因自我给药消退率和随后重新获得率的影响。与溶剂相比，消退训练前0.5小时用30 mg/kg DCS预处理可减少大鼠达到消退标准的反应次数和潜伏期，但DCS剂量均未改变猴的这些指标。在这两个物种中，与不存在DCS的消退训练或不存在显式消退的DCS相比，在消退训练之前用更高剂量的DCS预处理显着减弱了可卡因自我给药的重新获得。此外，30 mg/kg DCS治疗伴随短暂处理（应激诱导）后立即，但不是6小时后消退训练衰减可卡因自我管理的大鼠重新获得。在猴的定量观察性研究中，10 mg/kg DCS无明显不良反应。结果表明，DCS增强了消退学习的巩固，以阻止大鼠和猴子重新获得可卡因自我给药。结果表明，DCS与暴露疗法相结合，可能构成可卡因复吸的临床管理的合理策略。
Augmentation of cue exposure (extinction) therapy with cognitive-enhancing pharmacotherapy may offer an effective strategy to combat cocaine relapse. To investigate this possibility at the preclinical level, rats and squirrel monkeys were trained to self-administer cocaine paired with a brief visual cue. Lever pressing was subsequently extinguished by withholding cocaine injections while maintaining response-contingent presentations of the cue. The glycine partial agonist D-cycloserine (DCS; 15 and 30 mg/kg in rats, 3 and 10 mg/kg in monkeys) was evaluated for its effects on the rate of extinction and subsequent reacquisition of cocaine self-administration. Compared to vehicle, pretreatment with 30 mg/kg DCS 0.5 hr before extinction training reduced the number of responses and latency to reach the extinction criterion in rats, but neither dose of DCS altered these measures in monkeys. In both species pretreatment with the higher dose of DCS before extinction training significantly attenuated reacquisition of cocaine self-administration compared to either extinction training in the absence of DCS or DCS in the absence of explicit extinction. Furthermore, treatment with 30 mg/kg DCS accompanied by brief handling (a stress induction) immediately after but not 6 hr after extinction training attenuated reacquisition of cocaine self-administration in rats. No adverse effects of 10 mg/kg DCS were evident in quantitative observational studies in monkeys. The results suggest that DCS augmented consolidation of extinction learning to deter reacquisition of cocaine self-administration in rats and monkeys. The results suggest that DCS combined with exposure therapy may constitute a rational strategy for the clinical management of cocaine relapse.
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影响因子：
--
作者：
Hofmann, SG;Meuret, AE;Otto, MW
通讯作者：
Otto, MW
影响因子：
2.7
作者：
Hui, Isabel R.;Hui, Gabriel K.;Weinberger, Norman M.
通讯作者：
Weinberger, Norman M.
影响因子：
10.6
作者：
Franklin, TR;Acton, PD;Childress, AR
通讯作者：
Childress, AR
影响因子：
2.7
作者：
Feltenstein, Matthew W.;See, Ronald E.
通讯作者：
See, Ronald E.
影响因子：
10.6
作者：
Davis, Michael;Ressler, Kerry;Richardson, Rick
通讯作者：
Richardson, Rick