Department of Psychological and Brain Sciences & Neuroscience and Behavior Graduate Program, University of Massachusetts Amherst, Amherst, MA, 01003, USA.
Brain Health Institute, Rutgers University and Rutgers Biomedical and Health Sciences, Piscataway, NJ, 08854, USA.
Psychopharmacology (Berl). 2023 Mar;240(3):575-594. doi: 10.1007/s00213-022-06287-2. Epub 2022 Dec 5.
The prefrontal cortex is critical for execution and inhibition of reward seeking. Neural manipulation of rodent medial prefrontal cortex (mPFC) subregions differentially impacts execution and inhibition of cocaine seeking. Dorsal, or prelimbic (PL), and ventral, or infralimbic (IL) mPFC are implicated in cocaine seeking or extinction of cocaine seeking, respectively. This differentiation is not seen across all studies, indicating that further research is needed to understand specific mPFC contributions to drug seeking.
We recorded neuronal activity in mPFC subregions during cocaine self-administration, extinction, and cue- and cocaine-induced reinstatement of cocaine seeking.
Both PL and IL neurons were phasically responsive around lever presses during cocaine self-administration, and activity in both areas was reduced during extinction. During both cue- and, to a greater extent, cocaine-induced reinstatement, PL neurons exhibited significantly elevated responses, in line with previous studies demonstrating a role for the region in relapse. The enhanced PL signaling in cocaine-induced reinstatement was driven by strong excitation and inhibition in different groups of neurons. Both of these response types were stronger in PL vs. IL neurons. Finally, we observed tonic changes in activity in all tasks phases, reflecting both session-long contextual modulation as well as minute-to-minute activity changes that were highly correlated with brain cocaine levels and motivation associated with cocaine seeking.
Although some differences were observed between PL and IL neuron activity across sessions, we found no evidence of a go/stop dichotomy in PL/IL function. Instead, our results demonstrate temporally heterogeneous prefrontal signaling during cocaine seeking and extinction in both PL and IL, revealing novel and complex functions for both regions during these behaviors. This combination of findings argues that mPFC neurons, in both PL and IL, provide multifaceted contributions to the regulation of drug seeking and addiction.
前额皮质对于执行和抑制奖励寻求至关重要。对啮齿动物内侧前额皮质（mPFC）亚区的神经操纵会对可卡因寻求的执行和抑制产生不同的影响。背侧（或前扣带皮层，PL）和腹侧（或下边缘皮层，IL）mPFC 分别与可卡因寻求或可卡因寻求的消退有关。并非所有研究都能看到这种分化，这表明需要进一步研究以了解 mPFC 对药物寻求的具体贡献。
我们在可卡因自我给药、消退和线索及可卡因诱导的可卡因寻求复燃期间记录了 mPFC 亚区的神经元活动。
PL 和 IL 神经元在可卡因自我给药期间围绕杠杆按压呈相位反应，并且在消退期间这两个区域的活动都减少。在线索和更广泛的可卡因诱导复燃期间，PL 神经元表现出显著增强的反应，这与先前研究表明该区域在复发中的作用一致。PL 信号在可卡因诱导复燃中的增强是由不同神经元群的强烈兴奋和抑制驱动的。这两种反应类型在 PL 中比在 IL 中更强。最后，我们观察到在所有任务阶段的活动都发生了紧张变化，反映了长期的环境调节以及与大脑可卡因水平和与可卡因寻求相关的动机高度相关的分钟到分钟的活动变化。
尽管在整个实验过程中观察到 PL 和 IL 神经元活动之间存在一些差异，但我们没有发现 PL/IL 功能中存在“是/否”二分法的证据。相反，我们的结果表明，在 PL 和 IL 中，可卡因寻求和消退期间存在时间上异质的前额叶信号，揭示了这两个区域在这些行为中具有新颖而复杂的功能。这些发现的综合表明，mPFC 神经元，无论是在 PL 还是 IL 中，都对药物寻求和成瘾的调节提供了多方面的贡献。
