A non-invasive gating device for continuous drug delivery that allows control over the timing and duration of spontaneous opiate withdrawal
A non-invasive gating device for continuous drug delivery that allows control over the timing and duration of spontaneous opiate withdrawal
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DOI：
10.1016/j.jneumeth.2003.12.008
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发表时间：
2004-05-30
影响因子：
3
通讯作者：
Koob, GF
中科院分区：
文献类型：
--
作者：
Azar, MR;Ahmed, SH;Koob, GF
实验室动物中的阿片依赖通常通过两种方法诱导：（1）皮下（s.c.）插入吗啡丸，和（2）每天注射增加剂量的阿片类药物。虽然这两种方法都能可靠地诱导阿片类药物依赖，但它们不允许一个人停药。并随后用最小侵入性方法重新建立稳态阿片剂血浆水平。我们开发了一种“开-关”铜绿装置，用于通过标准渗透微型泵反复和非侵入性地打开或关闭阿片剂递送。利用纳洛酮（NAL）诱发的戒断体征和体重指数（BMI）作为戒断指标，对该“装置”的可靠性进行了测试。大鼠植入装有门控装置的渗透微型泵，含有海洛因（每天2.66毫克）。手术后三天。通过NAL（0.3mg/kg）每48 μ l诱发戒断的躯体体征，微泵门控为ON或OFF。对于BMI，通过每48小时关闭和打开门控装置重复（3次）诱导自发戒断。每天06：00至22：00，每4小时测量一次体重。结果表明，当门控装置开启时，NAL诱发强烈的躯体戒断症状，而当门控装置关闭时，这种效应几乎消失。BMI迅速下降后，门控设备被关闭，最大的体重减轻发生在12小时后关闭的位置，并逐渐恢复到基线值后，门控设备被打开。这些结果表明，有效性的“开-关”门控设备的非侵入性和反复诱导身体依赖阿片类药物在一段较长的时间。(C)2004 Elsevier B. V.保留所有权利。
Opiate dependence in laboratory animals is commonly induced by two methods: (1) subcutaneous (s.c.) insertion of morphine pellets, and (2) daily injections of increasing doses of opiates. While both of these methods reliably induce opiate dependence, they do not allow one to discontinue. and subsequently reestablish steady state opiate plasma levels with minimal invasive procedures. We developed an "ON-OFF" patina device for repeatedly and non-invasively turning ON or OFF opiate delivery by standard osmotic minipumps. The reliability of this "device" was tested utilizing naloxone (NAL)-precipitated somatic signs of withdrawal, and body mass index (BMI) as measures of withdrawal. Rats were implanted with osmotic minipumps equipped with the gating device, containing heroin (2.66 mg per day). Three days after surgery. somatic signs of withdrawal were precipitated every 48 It by NAL (0.3 mg/kg), with minipumps gated ON or OFF. For BMI, spontaneous withdrawal was repeatedly (three times) induced by turning OFF and ON the gating devices every 48 h. Body weights were measured every 4 h from 06:00 to 22:00 h daily. Results show that NAL precipitated intense somatic signs of withdrawal when gating devices were ON. This effect vas almost abolished when gating devices were OFF. BMI rapidly decreased after the gating devices were turned OFF with maximum weight loss occuring 12 h post-OFF position, and gradually returning to baseline values after gating devices were turned back ON. These results demonstrate the validity of the "ON-OFF" gating device for non-invasively and repeatedly inducing physical dependence to opiates over a prolonged time. (C) 2004 Elsevier B.V. All rights reserved.