The Institute of Mental Psychology, School of Health Management, The Affiliated Brain Hospital (Guangzhou Huiai Hospital), Guangzhou Medical University, Guangzhou 510370, China.
Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan Medical School, Sun Yat-sen University, 74 Zhongshan Road 2, Guangzhou 510080, China.
Sci Adv. 2023 Jun 23;9(25):eadg5849. doi: 10.1126/sciadv.adg5849.
The association between rewarding and drug-related memory is a leading factor for the formation of addiction, yet the neural circuits underlying the association remain unclear. Here, we showed that the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) integrated rewarding and environmental memory information by two different receiving projections from ventral tegmental area (VTA) and nucleus accumbens shell region (NAcSh) to mediate the acquisition of morphine conditioned place preference (CPP). A projection from the VTA GABAergic neurons (VTA) to the IPAC lateral region GABAergic neurons (IPACL) mediated the effect of morphine rewarding, whereas the pathway from NAcSh dopamine receptor 1-expressing neurons (NAcSh) to the IPAC medial region GABAergic neurons (IPACM) was involved in the acquisition of environmental memory. These findings demonstrated that the distinct IPAC circuits VTAIPACL and NAcShIPACM were attributable to the rewarding and environmental memory during the acquisition of morphine CPP, respectively, and provided the circuit-based potential targets for preventing and treating opioid addiction.
奖赏与药物相关记忆之间的关联是成瘾形成的主要因素，但支持这种关联的神经回路仍不清楚。在这里，我们表明，前连合后肢间核（IPAC）通过来自腹侧被盖区（VTA）和伏隔核壳区（NAcSh）的两个不同接收投射，整合了奖赏和环境记忆信息，介导了吗啡条件位置偏好（CPP）的获得。来自 VTA GABA 能神经元（VTA）投射到 IPAC 侧区 GABA 能神经元（IPACL）的投射介导了吗啡奖赏的作用，而来自 NAcSh 多巴胺受体 1 表达神经元（NAcSh）投射到 IPAC 中区 GABA 能神经元（IPACM）的投射则参与了环境记忆的获得。这些发现表明，在吗啡 CPP 获得过程中，不同的 IPAC 回路 VTAIPACL 和 NAcShIPACM 分别归因于奖赏和环境记忆，为预防和治疗阿片类药物成瘾提供了基于回路的潜在靶点。
