Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Pharmacol Res. 2022 Oct;184:106463. doi: 10.1016/j.phrs.2022.106463. Epub 2022 Sep 23.
Stress alters the level of reward evaluation and seeking. However, the neural circuitry mechanisms underlying stress induced effects on natural reward seeking remain unclear. Here we report a septal-accumbens pathway that mediates the effects of acute stress on reward seeking suppression. We first established the sucrose oral self-administration paradigm and measured the effects of acute stress on reward seeking behavior after 21 days of abstinence. Both forced swimming stress and foot shock stress significantly suppressed the natural reward seeking. Among a variety of brain regions, intermediolateral septum (LSi) appear as a strong stress-responsive area containing abundant c-Fos positive cells; chemogenetic inactivation of LSi reinstated the reward seeking behavior. To elucidate the downstream targets receiving LSi projections, we combined pathway-specific retro-labeling and chemogenetic manipulation to confirm the involvement of LSi-nucleus accumbens (NAc) rather than the Ventral tegmental area (VTA) in mediating the observed behavioral responses. In conclusion, the septal-accumbal projection constitute a discrete circuit dictating the stress evoked alterations on reward seeking and may implicate in treatment of stress induced anhedonia.
压力会改变奖赏评价和寻求的水平。然而，压力引起的自然奖赏寻求抑制效应的神经回路机制仍不清楚。在这里，我们报告了一个隔-伏隔核通路，它介导了急性应激对奖赏寻求抑制的影响。我们首先建立了蔗糖口服自我给药范式，并在 21 天戒断后测量了急性应激对奖赏寻求行为的影响。强迫游泳应激和足底电击应激均显著抑制了自然奖赏寻求。在多种脑区中，中间隔核（LSi）是一个强烈的应激反应区域，包含丰富的 c-Fos 阳性细胞；LSi 的化学遗传失活恢复了奖赏寻求行为。为了阐明接收 LSi 投射的下游靶点，我们结合了特定通路的逆行标记和化学遗传操作，以确认 LSi-伏隔核（NAc）而不是腹侧被盖区（VTA）参与介导观察到的行为反应。总之，隔核-伏隔核投射构成了一个离散的回路，决定了应激引起的奖赏寻求的改变，并可能参与治疗应激引起的快感缺失。
