Inactivation of the central nucleus of the amygdala reduces the effect of punishment on cocaine self-administration in rats.
Inactivation of the central nucleus of the amygdala reduces the effect of punishment on cocaine self-administration in rats.
复制标题
杏仁核中央核的失活降低了惩罚对大鼠可卡因自我给药的影响。
DOI：
10.1111/j.1460-9568.2012.08000.x
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Sun,WenLin
中科院分区：
文献类型：
--
作者：
Xue,YueQiang;Steketee,JefferyD;Sun,WenLin
持续使用可卡因，尽管有负面影响，是可卡因成瘾的标志。其中一个后果是惩罚，社会经常使用惩罚来遏制可卡因的使用。不幸的是，我们对惩罚可卡因使用的监管机制知之甚少。可卡因成瘾者继续使用可卡因，尽管可能受到严厉的惩罚，这一事实表明，这一机制可能受到了损害。预计这种损害将严重促进可卡因的强迫使用。本研究旨在验证杏仁核（CeN）在这种调节中起关键作用的假设。为此，大鼠被训练按下杠杆，在链式计划下自我施用可卡因：一个杠杆（可卡因寻求杠杆）上的反应导致进入另一个杠杆（可卡因摄取杠杆），可卡因和线索加强了反应。此后，寻求杠杆上的反应受到脚震的惩罚，概率为0.5。惩罚以强度依赖的方式显著抑制了自我管理（SA）。有趣的是，每天训练6小时（扩展访问）而不是2小时（有限访问）的大鼠表现出对较低强度惩罚的抵抗力。在两组中，CeNs的失活都诱导了强大的抗惩罚效应。这些数据提供的证据表明，CeN是一个重要的神经基板参与监管的惩罚可卡因SA。长期服用可卡因SA的大鼠似乎对惩罚不太敏感。这种敏感性的降低可能是由于延长的可卡因SA在CeN中引起的神经可塑性变化。
Continued cocaine use despite the negative consequences is a hallmark of cocaine addiction. One such consequence is punishment, which is often used by society to curb cocaine use. Unfortunately, we know little about the mechanism involved in regulation by punishment of cocaine use. The fact that cocaine addicts continue to use cocaine despite potentially severe punishment suggests that the mechanism may be impaired. Such impairment is expected to critically contribute to compulsive cocaine use. This study was aimed at testing the hypothesis that the central nucleus of the amygdala (CeN) plays a critical role in such regulation. To this end, rats were trained to press a lever to self‐administer cocaine under a chained schedule: a response on one lever (cocaine‐seeking lever) led to access to the other lever (cocaine‐taking lever), on which a response was reinforced by cocaine and cues. Thereafter, responses on the seeking lever were punished by footshock with a probability of 0.5. Cocaine self‐administration (SA) was significantly suppressed by punishment in an intensity‐dependent manner. Interestingly, rats trained with daily 6‐h (extended access) but not 2‐h (limited access) sessions showed resistance to the lower intensity of punishment. Inactivation of the CeN induced a robust anti‐punishment effect in both groups. These data provided evidence that the CeN is a critical neural substrate involved in regulation by punishment of cocaine SA. Rats with a history of extended cocaine SA appeared to be less sensitive to punishment. The decreased sensitivity could result from the neuroplastic changes induced by extended cocaine SA in the CeN.