Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA; Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC, USA.
Department of Psychology, East Tennessee State University, Johnson City, TN, USA.
Neuropharmacology. 2017 Apr;116:208-223. doi: 10.1016/j.neuropharm.2016.12.020. Epub 2016 Dec 22.
Pavlovian conditioned stimuli can acquire incentive motivational properties, and this phenomenon can be measured in animals using Pavlovian conditioned approach behavior. Drugs of abuse can influence the expression of this behavior, and nicotine in particular exhibits incentive amplifying effects. Both conditioned approach behavior and drug abuse rely on overlapping corticolimbic circuitry. We hypothesize that the orbitofrontal cortex (OFC) regulates conditioned approach, and that one site of nicotine action is in the OFC where it reduces cortical output. To test this, we repeatedly exposed rats to 0.4 mg/kg nicotine (s.c.) during training and then pharmacologically inactivated the lateral OFC or performed in vivo electrophysiological recordings of lateral OFC neurons in the presence or absence of nicotine. In Experiment 1, animals were trained in a Pavlovian conditioning paradigm and behavior was evaluated after inactivation of the OFC by microinfusion of the GABA agonists baclofen and muscimol. In Experiment 2, we monitored phasic firing of OFC neurons during Pavlovian conditioning sessions. Nicotine reliably enhanced conditioned responding to the conditioned cue, and inactivation of the OFC reduced conditioned responding, especially the sign-tracking response. OFC neurons exhibited phasic excitations to cue presentation and during goal tracking, and nicotine acutely blunted this phasic neuronal firing. When nicotine was withheld, both conditioned responding and phasic firing in the OFC returned to the level of controls. These results suggest that the OFC is recruited for the expression of conditioned responses, and that nicotine acutely influences this behavior by reducing phasic firing in the OFC.
巴甫洛夫条件刺激可以获得激励动机属性，并且可以使用巴甫洛夫条件接近行为在动物中测量这种现象。滥用药物会影响这种行为的表达，而尼古丁尤其表现出激励放大效应。条件接近行为和药物滥用都依赖于重叠的皮质边缘回路。我们假设眶额皮层（OFC）调节条件接近，而尼古丁的作用部位之一是 OFC，在那里它减少皮质输出。为了验证这一点，我们在训练期间反复向大鼠暴露于 0.4mg/kg 尼古丁（sc），然后用侧眶额皮质的 GABA 激动剂巴氯芬和毒蕈碱进行药理学失活，或在存在或不存在尼古丁的情况下进行侧眶额皮质神经元的体内电生理记录。在实验 1 中，动物在巴甫洛夫条件反射范式中接受训练，然后通过微注射 GABA 激动剂巴氯芬和毒蕈碱对 OFC 进行失活，评估行为。在实验 2 中，我们在巴甫洛夫条件反射期间监测 OFC 神经元的相位放电。尼古丁可靠地增强了对条件线索的条件反应，而 OFC 的失活减少了条件反应，特别是标志跟踪反应。OFC 神经元在线索呈现和目标跟踪期间表现出相位兴奋，而尼古丁急性地使这种相位神经元放电变钝。当尼古丁被剥夺时，OFC 的条件反应和相位放电都恢复到对照水平。这些结果表明，OFC 被招募用于表达条件反应，而尼古丁通过减少 OFC 中的相位放电急性影响这种行为。
