Morphine-induced conditioned place preference in rhesus monkeys: Resistance to inactivation of insula and extinction

Morphine-induced conditioned place preference in rhesus monkeys: Resistance to inactivation of insula and extinction
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吗啡诱导的恒河猴条件性位置偏好:对岛叶失活和灭绝的抵抗

DOI:
10.1016/j.nlm.2016.04.005
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发表时间:
2016-05
影响因子:
2.7
通讯作者:
JianHong Wang
JianHong Wang
中科院分区:
心理学4区
文献类型:
--
作者:
XuJun Wu;Ning Zhao;Fan Bai;ChuanYu Li;CiRong Liu;JingKuan Wei;Wei Zong;LiXin Yang;Andrey E.Ryabinin;YuanYe Ma;JianHong Wang

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药物成瘾者会对药物相关线索产生强烈的渴望。使用药理学或行为学方法减弱这些反应可以帮助从成瘾中恢复。线索诱导的药物寻求可以使用条件位置偏好程序(CPP)建模。我们的前期工作表明,增加吗啡剂量可以诱导恒河猴产生条件性位置偏爱(CPP)。在这里,我们研究了吗啡诱导的CPP的表达是否可以通过抑制岛叶皮质的活性或通过反复暴露于CPP测试来减弱。已证实,该病毒与几种滥用药物成瘾有关。为了测试其在吗啡CPP中的作用,将双侧插管植入7只成年猴的延髓中。使用偏置装置,通过肌内注射每只猴递增剂量(1.5、3.0和4.5 mg/kg)的吗啡建立CPP。在猴建立吗啡CPP后,采用受试者内设计,在CPP后处理试验(表达)之前,通过双侧微量注射5%利多卡因(40 μl)使其胰岛可逆性失活。与盐水注射相比,利多卡因的微量注射未能影响CPP表达。随后,我们在接下来的75.0 ± 0.2个月内对这些猴子进行了6次CPP测试,研究了吗啡相关记忆。虽然偏好评分显示出下降的趋势,重复测试,吗啡诱导的CPP保持,即使在最后一次测试中进行的75个月后的条件。这一观察结果表明,吗啡诱导的记忆在恒河猴中对消退具有很强的抵抗力。虽然这些数据并没有证实吗啡诱导的CPP中的药物相关记忆的参与,我们的观察,即药物相关的记忆可以保持超过6年的无药吗啡的初步经验,具有重要意义的药物成瘾使用消退疗法的治疗。
Drug addicts experience strong craving episodes in response to drug-associated cues. Attenuating these responses using pharmacological or behavioral approaches could aid recovery from addiction. Cue-induced drug seeking can be modeled using the conditioned place preference procedure (CPP). Our previous work showed that conditioned place preference (CPP) can be induced by administration of increasing doses of morphine in rhesus monkeys. Here, we investigated whether expression of morphine-induced CPP can be attenuated by inhibiting activity of insular cortex or by repeated unreinforced exposures to the CPP test. The insula has been demonstrated to be involved in addiction to several drugs of abuse. To test its role in morphine CPP, bilateral cannulae were implanted into the insula in seven adult monkeys. The CPP was established using a biased apparatus by intramuscular injections of morphine at increasing doses (1.5, 3.0 and 4.5 mg/kg) for each monkey. After the monkeys established morphine CPP, their insulae were reversibly inactivated by bilateral microinjection with 5% lidocaine (40 μl) prior to the post-conditioning test (expression) of CPP using a within-subject design. The microinjections of lidocaine failed to affect CPP expression when compared to saline injections. We subsequently investigated morphine-associated memory during six episodes of CPP tests performed in these monkeys over the following 75.0 ± 0.2 months. While the preference score showed a declining trend with repeated testing, morphine-induced CPP was maintained even on the last test performed at 75 months post-conditioning. This observation indicated strong resistance of morphine-induced memories to extinction in rhesus monkeys. Although these data do not confirm involvement of insula in morphine-induced CPP, our observation that drug-associated memories can be maintained over six drug-free years following initial experience with morphine has important implications for treatment of drug addiction using extinction therapy.
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