Behavioral Neuroscience Branch, Intramural Research Program, NIDA, Baltimore, Maryland 21224
Behavioral Neuroscience Branch, Intramural Research Program, NIDA, Baltimore, Maryland 21224.
J Neurosci. 2018 Jan 3;38(1):51-59. doi: 10.1523/JNEUROSCI.2521-17.2017.
Studies using the renewal procedure showed that basolateral amygdala (BLA) inactivation inhibits context-induced relapse to cocaine-seeking after extinction. Here, we determined whether BLA inactivation would also inhibit context-induced relapse after drug-reinforced responding is suppressed by punishment, an animal model of human relapse after self-imposed abstinence due to adverse consequences of drug use. We also determined the effect of central amygdala (CeA) inactivation on context-induced relapse.We trained rats to self-administer cocaine for 12 d (6 h/d) in Context A and then exposed them to either extinction or punishment training for 8 d in Context B. During punishment, 50% of cocaine-reinforced lever-presses produced an aversive footshock of increasing intensity (0.1-0.5 or 0.7 mA). We then tested the rats for relapse to cocaine seeking in the absence of cocaine or shock in Contexts A and B after BLA or CeA injections of vehicle or GABA agonists (muscimol-baclofen). We then retrained the rats for cocaine self-administration in Context A, repunished or re-extinguished lever pressing in Context B, and retested for relapse after BLA or CeA inactivation.BLA or CeA inactivation context-induced relapse in Context A after extinction in Context B. BLA, but not CeA, inactivation context-induced relapse in Context A after punishment in Context B. BLA or CeA inactivation provoked relapse in Context B after punishment but not extinction. Results demonstrate that amygdala's role in relapse depends on the method used to achieve abstinence and highlights the importance of studying relapse under abstinence conditions that more closely mimic the human condition. Relapse to drug use during abstinence is often provoked by re-exposure to the drug self-administration environment or context. Studies using the established extinction-reinstatement rodent model of drug relapse have shown that inactivation of the basolateral amygdala inhibits context-induced drug relapse after extinction of the drug-reinforced responding. Here, we determined whether basolateral amygdala inactivation would also inhibit relapse after drug-reinforced responding is suppressed by punishment, a model of human relapse after self-imposed abstinence. Unexpectedly, we found that basolateral amygdala inactivation had opposite effects on relapse provoked by re-exposure to the drug self-administration environment after extinction versus punishment. Our results demonstrate that depending on the historical conditions that lead to abstinence, amygdala activity can either promote or inhibit relapse.
研究使用更新程序表明，基底外侧杏仁核（BLA）失活可抑制可卡因寻求消退后的情境诱导复吸。在这里，我们确定 BLA 失活是否也会抑制药物强化反应受到惩罚后情境诱导的复吸，这是一种由于药物使用的不良后果而导致自我禁欲后的人类复吸的动物模型。我们还确定了中央杏仁核（CeA）失活对情境诱导复吸的影响。我们训练大鼠在情境 A 中自我给予可卡因 12 天（每天 6 小时），然后在情境 B 中进行消退或惩罚训练 8 天。在惩罚期间，50%的可卡因强化杠杆按压会产生递增强度的厌恶性足部电击（0.1-0.5 或 0.7 mA）。然后，我们在没有可卡因或电击的情况下，在情境 A 和 B 中测试大鼠在 BLA 或 CeA 注射载体或 GABA 激动剂（毒蕈碱-巴氯芬）后的可卡因寻求复吸情况。然后，我们重新训练大鼠在情境 A 中自我给予可卡因，在情境 B 中重新惩罚或重新消退杠杆按压，并在 BLA 或 CeA 失活后再次测试复吸情况。BLA 或 CeA 失活可抑制消退后情境 A 中的情境诱导复吸。BLA 但不是 CeA 失活可抑制惩罚后情境 A 中的情境诱导复吸。BLA 或 CeA 失活在惩罚后但不在消退后引起情境 B 中的复吸。结果表明，杏仁核在复吸中的作用取决于实现禁欲的方法，并强调了在更接近人类状况的禁欲条件下研究复吸的重要性。禁欲期间对药物的复吸通常是由重新暴露于药物自我给药环境或情境引起的。使用已建立的药物复吸的消退-再恢复啮齿动物模型的研究表明，基底外侧杏仁核的失活可抑制药物强化反应消退后的情境诱导药物复吸。在这里，我们确定基底外侧杏仁核失活是否也会抑制药物强化反应受到惩罚后的复吸，这是一种由于药物使用的不良后果而导致自我禁欲后的人类复吸模型。出乎意料的是，我们发现基底外侧杏仁核失活对消退后重新暴露于药物自我给药环境引起的复吸和惩罚后引起的复吸有相反的影响。我们的结果表明，根据导致禁欲的历史条件，杏仁核活动可以促进或抑制复吸。
