The infralimbic and prelimbic cortices contribute to the inhibitory control of cocaine-seeking behavior during a discriminative stimulus task in rats.
The infralimbic and prelimbic cortices contribute to the inhibitory control of cocaine-seeking behavior during a discriminative stimulus task in rats.
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DOI：
10.1111/adb.12434
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发表时间：
2017-11
影响因子：
3.4
通讯作者：
LaLumiere RT
中科院分区：
文献类型：
--
作者：
Gutman AL;Ewald VA;Cosme CV;Worth WR;LaLumiere RT
内侧前额叶皮层的边缘下区和边缘前区（分别为IL和PL）调节对药物寻求行为的控制。然而，他们在可卡因寻求在歧视性刺激（DS）为基础的自我管理任务的作用还不清楚。为了解决这个问题，雄性Sprague-Dawley大鼠接受了DS任务的训练，其中在逐个试验的基础上，DS+表示杠杆按压会产生可卡因输注，而不同的DS-表示杠杆按压不会产生任何东西。通过GABA受体激活的IL和PL失活降低了DS-试验的表现准确性和解除了行为反应，导致DS-呈现期间更大的杠杆按压。这伴随着获得的可卡因输注的减少，这一发现在随后的实验中使用标准FR 1可卡因自我给药范例得到证实。我们使用食物奖励重复了DS研究，发现每个区域的失活降低了表现准确性，但对获得的食物颗粒总数没有影响。可卡因DS任务的其他实验发现，IL中的多巴胺受体阻断剂（而不是PL）降低了DS-试验的表现准确性并解除了行为反应的抑制，而IL和PL中的AMPA受体阻断剂对表现准确性没有影响。这些发现强烈表明，在基于DS的自我给药任务中，大鼠必须在逐个试验的基础上主动决定是否参与杠杆按压（DS+）或抑制杠杆按压（DS-），IL和PL都有助于药物寻求行为的抑制控制。
The infralimbic and prelimbic (IL and PL, respectively) regions of the medial prefrontal cortex regulate the control of drug-seeking behavior. However, their roles in cocaine seeking in a discriminative stimulus (DS)-based self-administration task are unclear. To address this issue, male Sprague-Dawley rats were trained on a DS task in which, on a trial-by-trial basis, a DS+ indicated that a lever press would produce a cocaine infusion, whereas a distinct DS− indicated that a lever press would produce nothing. IL and PL inactivation via GABA receptor activation decreased performance accuracy and disinhibited behavioral responding on DS− trials, resulting in greater lever pressing during the DS− presentation. This was accompanied by a decrease in cocaine infusions obtained, a finding confirmed in a subsequent experiment using a standard FR1 cocaine self-administration paradigm. We repeated the DS study using a food reward and found that inactivation of each region decreased performance accuracy but had no effect on the total number of food pellets earned. Additional experiments with the cocaine DS task found that dopamine receptor blockade in the IL, but not PL, reduced performance accuracy and disinhibited behavioral responding on DS− trials, whereas AMPA receptor blockade in the IL and PL had no effect on performance accuracy. These findings strongly suggest that, in a DS-based self-administration task in which rats must actively decide whether to engage in lever pressing (DS+) or withhold lever pressing (DS−) on a trial-by-trial basis, both the IL and PL contribute to the inhibitory control of drug-seeking behavior.