Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
Brain Health Institute, Rutgers University and Rutgers Biomedical and Health Sciences, Piscataway, NJ, USA.
Neuropsychopharmacology. 2018 Apr;43(5):987-1000. doi: 10.1038/npp.2017.144. Epub 2017 Jul 11.
Lateral septum (LS) has re-emerged as an important structure in reward and addiction; however, LS afferents that drive addiction behaviors are unknown. Here, we used a modified self-administration/reinstatement procedure combined with anatomical, pharmacological, and chemogenetic techniques to characterize LS, and hippocampal inputs to LS, in two established triggers of drug relapse-context- and cue-induced reinstatement of cocaine seeking. We found that inactivation of LS neurons attenuated both context- and cue-induced reinstatement of cocaine seeking. However, dorsal hippocampus inputs to LS showed enhanced neuronal activation (as measured by Fos expression) during context-induced, but not cue-induced reinstatement. Additionally, chemogenetic inhibition of dorsal, but not ventral, hippocampal inputs to LS specifically attenuated context-induced reinstatement. Together these findings elucidate the importance of LS in reinstatement of cocaine seeking, and indicate that dorsal hippocampal inputs to LS mediate context-, but not cue-induced, reinstatement of cocaine seeking.
外侧隔核 (LS) 作为奖赏和成瘾的一个重要结构重新出现；然而，驱动成瘾行为的 LS 传入尚不清楚。在这里，我们使用改良的自我给药/再巩固程序，结合解剖学、药理学和化学遗传技术，来描述 LS 以及海马传入 LS 在两种已建立的药物复燃触发因素——情境和线索诱导可卡因寻求的再巩固中的作用。我们发现 LS 神经元的失活减弱了情境和线索诱导的可卡因寻求的再巩固。然而，在情境诱导而非线索诱导的再巩固过程中，LS 的背侧海马传入显示出增强的神经元激活（如 Fos 表达所测量的）。此外，化学遗传抑制 LS 的背侧而非腹侧海马传入特异性减弱了情境诱导的再巩固。这些发现共同阐明了 LS 在可卡因寻求再巩固中的重要性，并表明 LS 的背侧海马传入介导了情境而非线索诱导的可卡因寻求的再巩固。
