Contextual memory driven by abused drugs such as opiates has a central role in maintenance and relapse of drug-taking behaviors. Although dopamine (DA) signaling favors memory storage and retrieval via regulation of hippocampal-prefrontal connectivity, its role in modulating opiate-associated contextual memory is largely unknown. Here, we report roles of DA signaling within the hippocampal-prefrontal circuit for opiate-related memories. Combining-conditioned place preference (CPP) with molecular analyses, we investigated the DA D1 receptor (D1R) and extracellular signal-regulated kinase (ERK)-cAMP-response element binding protein (CREB) signaling, as well as DA D2 receptor (D2R) and protein kinase B (PKB or Akt)/glycogen synthase kinase 3 (GSK3) signaling in the ventral hippocampus (vHip) and medial prefrontal cortex (mPFC) during the formation of opiate-related associative memories. Morphine-CPP acquisition increased the activity of the D1R-ERK-CREB pathway in both the vHip and mPFC. Morphine-CPP reinstatement was associated with the D2R-mediated hyperactive GSK3 via Akt inhibition in the vHip and PFC. Furthermore, integrated D1R-ERK-CREB and D2R-Akt-GSK3 pathways in the vHip-mPFC circuit are required for the acquisition and retrieval of the morphine contextual memory, respectively. Moreover, blockage of D1R or D2R signaling could alleviate normal Hip-dependent spatial memory. These results suggest that D1R and D2R signaling are differentially involved in the acquisition and retrieval of morphine contextual memory, and DA signaling in the vHip-mPFC connection contributes to morphine-associated and normal memory, largely depending on opiate exposure states.

中文翻译：

---

阿片类药物相关的上下文记忆形成和检索受到海马前额叶连接中多巴胺 D1 和 D2 信号传导的不同调节。

由阿片类药物等滥用药物驱动的情境记忆在吸毒行为的维持和复发中起着核心作用。尽管多巴胺 (DA) 信号通过调节海马前额叶连接有利于记忆存储和检索，但其在调节阿片类药物相关上下文记忆中的作用在很大程度上是未知的。在这里，我们报告了 DA 信号在海马前额叶回路中对阿片类药物相关记忆的作用。结合条件位置偏好 (CPP) 和分子分析，我们研究了 DA D1 受体 (D1R) 和细胞外信号调节激酶 (ERK)-cAMP 反应元件结合蛋白 (CREB) 信号传导，以及阿片类药物相关联想记忆形成过程中腹侧海马 (vHip) 和内侧前额叶皮层 (mPFC) 中的 DA D2 受体 (D2R) 和蛋白激酶 B (PKB 或 Akt)/糖原合酶激酶 3 (GSK3) 信号传导. 吗啡-CPP 的获得增加了 vHip 和 mPFC 中 D1R-ERK-CREB ​​通路的活性。通过 vHip 和 PFC 中的 Akt 抑制，吗啡-CPP 恢复与 D2R 介导的过度活跃的 GSK3 相关。此外，分别需要 vHip-mPFC 电路中集成的 D1R-ERK-CREB ​​和 D2R-Akt-GSK3 通路来获取和检索吗啡上下文记忆。此外，阻断 D1R 或 D2R 信号可以减轻正常的髋关节依赖性空间记忆。