Basolateral amygdala inactivation abolishes conditioned stimulus- and heroin-induced reinstatement of extinguished heroin-seeking behavior in rats
Basolateral amygdala inactivation abolishes conditioned stimulus- and heroin-induced reinstatement of extinguished heroin-seeking behavior in rats
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DOI：
10.1007/s00213-001-0997-7
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发表时间：
2002-04-01
影响因子：
3.4
通讯作者：
See, RE
中科院分区：
文献类型：
--
作者：
Fuchs, RA;See, RE
理论基础：药物配对的刺激会在吸毒者中引发药物渴望和复发，并在大鼠中引发药物寻找行为。杏仁基底外侧核(BLA)的功能完整性是恢复可卡因条件刺激引起的寻找可卡因行为所必需的，但不是可卡因本身所致。然而，目前尚不清楚BLA是否在恢复海洛因寻觅行为方面发挥了类似的作用。目的：研究河豚毒素(TTX)诱导的血乳酸失活对海洛因刺激和条件性恢复海洛因寻找行为的影响。方法：训练大鼠按下控制杆进行静脉注射海洛因(维持剂量为25杯/次)，并在每天3小时的训练中呈现轻度刺激复合体。然后，在恢复测试之前，允许响应熄灭。消除的海洛因寻找行为(即在没有海洛因强化的情况下按下杠杆)的恢复是在仅呈现海洛因对刺激复合体的反应条件下进行的，然后跟随TTX(每侧5 ng/0.5毫升)或向BLA中注入载体。在另一组大鼠中，在注射生理盐水(SC)后，再用河豚毒素(TTX)或赋形剂注入血乳酸(BLA)，然后海洛因(0.25 mg/kg，SC)刺激后，测量恢复情况。结果：反应条件性呈现的刺激复合体和海洛因激发均能显著恢复被消除的寻找海洛因行为，而血乳酸灭活则使海洛因对刺激和海洛因激发的反应恢复能力消失。结论：这些发现表明，BLA是调节条件性和海洛因诱导的海洛因寻找行为恢复的神经回路的关键组成部分。此外，不同的神经底物可能会介导毒品引发的可卡因复发与海洛因寻找行为。
Rationale: Drug-paired stimuli elicit drug craving and relapse in addicts and drug-seeking behavior in rats. The functional integrity of the basolateral amygdala (BLA) is necessary for reinstatement of cocaine-seeking behavior elicited by cocaine-conditioned stimuli, but not by cocaine itself. It is unclear, however, whether the BLA plays a similar role in reinstatement of heroin-seeking behavior. Objectives: To this end, we examined the effects of tetrodotoxin (TTX)-induced inactivation of the BLA on conditioned and heroin-primed reinstatement of extinguished heroin-seeking behavior. Methods: Rats were trained to press a lever for IV infusions of heroin (maintenance dose of 25 mug/infusion) paired with presentations of a light-tone stimulus complex during daily 3-h sessions. Responding was then allowed to extinguish prior to reinstatement testing. Reinstatement of extinguished heroin-seeking behavior (i.e. lever pressing in the absence of heroin reinforcement) was measured in the presence of response-contingent presentation of the heroin-paired stimulus complex alone and then following TTX (5 ng/0.5 mul per side) or vehicle infused into the BLA. In a separate group of rats, reinstatement was measured after saline injection (SC) and then following heroin priming (0.25 mg/kg, SC) with TTX or vehicle infused into the BLA. Results: Both response contingent presentation of the stimulus complex and heroin priming significantly reinstated extinguished heroin-seeking behavior, and BLA inactivation abolished the ability of the heroin-paired stimuli and of heroin priming to reinstate responding. Conclusions: These findings suggests that the BLA is a critical component of the neural circuitry that mediates conditioned and heroin-induced reinstatement of heroin-seeking behavior. Furthermore, different neural substrates may mediate drug-primed relapse to cocaine versus heroin-seeking behavior.