Stress reinstates cocaine-seeking behavior after prolonged extinction and a drug-free period
Stress reinstates cocaine-seeking behavior after prolonged extinction and a drug-free period
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DOI：
10.1007/s002130050150
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发表时间：
1996-12-01
影响因子：
3.4
通讯作者：
Stewart, J
中科院分区：
文献类型：
--
作者：
Erb, S;Shaham, Y;Stewart, J
我们之前已经用复发的动物模型表明，急性暴露于间歇性足震应激可诱导大鼠恢复吸食海洛因的行为。在本研究中，我们报告了在自我使用可卡因的大鼠中，暴露于急性间歇性足部冲击应激可诱导在长时间的消失期和4至6周的无药期后恢复可卡因服用行为；一种与注射可卡因引起的效果相当的效果。最初允许动物自行给药盐酸可卡因（每次输注1.0 mg/kg，静脉注射），每次3小时/天，持续12天。随后，通过用生理盐水代替可卡因引入消灭条件，使杠杆按压导致静脉输注生理盐水而不是药物。灭绝条件一直维持到动物在3小时内做出15次或更少的反应，之后在每天的实验开始时给动物注射生理盐水，以建立10次或更少的基线反应。随后，在非偶然注射可卡因（2.0 mg/kg， IV）和暴露于间歇性足部休克（10分钟，0.5 mA, 0.5 s，平均关闭时间40秒）后，对动物进行生理盐水输注恢复反应的测试。在另外4至6周的禁药期后，再次进行恢复测试。在两组试验中均观察到足震和可卡因对可卡因吸食行为的恢复。这些结果扩展了本实验室先前的报告，即足震应激是大鼠药物服用行为恢复的有效刺激。
We have shown previously, using an animal model of relapse, that acute exposure to intermittent footshock stress induces reinstatement of heroin-taking behavior in rats. Here we report that in rats trained to self-administer cocaine, exposure to acute intermittent footshock stress induces reinstatement of cocaine-taking behavior after prolonged extinction sessions and after a 4- to 6-week drug-free period; an effect comparable to that induced by a priming injection of cocaine. Animals were initially allowed to self-administer cocaine HCl (1.0 mg/kg per infusion, IV) during one 3-h session/day for 12 days. Subsequently, extinction conditions were introduced by substituting saline for cocaine so that lever-pressing resulted in IV infusions of saline rather than of drug. Extinction conditions were maintained until animals made 15 responses or less in the 3 h, after which animals were given saline infusions at the start of each daily session to establish baseline responding of ten responses or less. Subsequently, animals were tested for reinstatement of responding for saline infusions following a non-contingent injection of cocaine (2.0 mg/kg, IV) and exposure to intermittent footshock (10 min, 0.5 mA, 0.5 s on, mean off period of 40 sec). After an additional 4- to 6-week drug-free period, tests for reinstatement were repeated. Reinstatement of cocaine-taking behavior was observed in both sets of tests in response to footshock and cocaine. These results extend previous reports from this laboratory that footshock stress is an effective stimulus for reinstatement of drug-taking behavior in the rat.