Long-lasting decreases in cocaine-reinforced behavior following treatment with the cholinesterase inhibitor tacrine in rats selectively bred for drug self-administration
Long-lasting decreases in cocaine-reinforced behavior following treatment with the cholinesterase inhibitor tacrine in rats selectively bred for drug self-administration
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DOI：
10.1016/j.pbb.2009.08.004
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发表时间：
2009-11-01
影响因子：
3.6
通讯作者：
Yang, Yungao
中科院分区：
文献类型：
--
作者：
Grasing, Kenneth;He, Shuangteng;Yang, Yungao
他克林是一种中枢作用、可逆的胆碱酯酶抑制剂，可增加突触乙酰胆碱（ACh）水平，并可增强多巴胺（DA）的作用。本研究旨在评估他克林对高水平自我给药大鼠（HS系）选择性繁殖的可卡因-rein强迫反应的影响。HS大鼠按固定比例5 （FR-5）自行给药不同剂量的可卡因。在四天的时间里，当动物在家庭笼中饲养（每天21小时）时，注射了载体或他克林（1.0、3.2或10 mg/kg-day）。他克林剂量依赖性地减少可卡因自我给药。他克林的作用在预处理20分钟内开始的自我给药（称为早期疗程）和在他克林停止给药后1至3天内开始的自我给药（晚期疗程）有所不同。他克林在后期对可卡因-相对于食物强化的HS大鼠和HS相对于近亲繁殖的大鼠的自我给药的减弱效力更大。在他克林治疗的HS大鼠的一个子集中，可卡因自我给药在一周内持续减少，比预处理基线水平减少80%以上，在此期间没有进一步给药。总之，用他克林预处理可以产生持久的衰减可卡因-rein强迫反应。Elsevier Inc.出版。
Tacrine is a centrally acting, reversible cholinesterase inhibitor that increases synaptic levels of acetylcholine (ACh) and can potentiate the actions of dopamine (DA). The present study was conducted to evaluate effects of tacrine on cocaine-rein forced responding in a rat line selectively bred for high levels of drug self-administration (the HS line). HS rats self-administered different doses of cocaine under a fixed-ratio-5 (FR-5) schedule. Over a four-day period, vehicle or tacrine (1.0, 3.2, or 10 mg/kg-day) was infused when animals were maintained in home cages (21 h per day). Tacrine dose-dependently decreased cocaine self-administration. Actions of tacrine differed for self-administration that was initiated within 20 min of pretreatment (described as early sessions), and for self-administration that occurred between one and three days after administration of tacrine was discontinued (late sessions). Tacrine's potency for attenuating self-administration during late sessions was greater for cocaine-relative to food-reinforcement in HS rats, and for HS relative to outbred rats. In a subset of tacrine-treated HS rats, cocaine self-administration was persistently attenuated by more than 80% from pretreatment baseline levels over a one-week period during which no further tacrine was administered. In summary, pretreatment with tacrine can produce a long-lasting attenuation of cocaine-rein forced responding. Published by Elsevier Inc.