Mesa Javier R, Wesson Daniel W, Schwendt Marek, Knackstedt Lori A
Department of Psychology, University of Florida, 114 Psychology, 945 Center Dr., Gainesville, FL 32611, USA.
Center for Addiction Research and Education, University of Florida, Gainesville, FL, USA.
Addict Neurosci. 2022 Dec;4. doi: 10.1016/j.addicn.2022.100031. Epub 2022 Jul 28.
A large body of research supports the notion that regions of the rodent frontal cortex regulate reinstatement of cocaine seeking after cessation of intravenous cocaine self-administration. However, earlier studies identifying the roles of medial (mPFC) and orbital prefrontal cortices (OFC) in reinstatement relied on pharmacological inactivation methods, which indiscriminately inhibited cells within a target region. Here, we first review the anatomical borders and pathways of the rat mPFC and OFC. Next, we compare and contrast findings from more recent cocaine seeking and reinstatement studies that used chemogenetics, optogenetics, or advanced tracing to manipulate specific local cell types or input/output projections of the mPFC and OFC subregions. We found that these studies largely corroborated the roles for mPFC subregions as ascribed by pharmacological inactivation studies. Namely, the prelimbic cortex generally drives cocaine seeking behaviors while the infralimbic cortex is recruited to inhibit cocaine seeking by extinction training but may contribute to seeking after prolonged abstinence. While the OFC remains understudied, we suggest it should not be overlooked, and, as with prelimbic and infralimbic cortices, we identify specific pathways of interest for future studies.
大量研究支持这样一种观点，即啮齿动物额叶皮质区域在静脉注射可卡因自我给药停止后调节可卡因觅求行为的恢复。然而，早期确定内侧前额叶皮质（mPFC）和眶前额叶皮质（OFC）在恢复中的作用的研究依赖于药理学失活方法，这种方法不加区分地抑制目标区域内的细胞。在这里，我们首先回顾大鼠mPFC和OFC的解剖边界和通路。接下来，我们比较和对比最近使用化学遗传学、光遗传学或先进示踪技术来操纵mPFC和OFC亚区域的特定局部细胞类型或输入/输出投射的可卡因觅求和恢复研究的结果。我们发现，这些研究在很大程度上证实了药理学失活研究所赋予mPFC亚区域的作用。具体而言，前边缘皮质通常驱动可卡因觅求行为，而边缘下皮质通过消退训练被招募来抑制可卡因觅求，但可能在长期禁欲后促成觅求行为。虽然OFC的研究仍然不足，但我们建议不应忽视它，并且与前边缘皮质和边缘下皮质一样，我们确定了未来研究感兴趣的特定通路。
