μ-opioid receptor (MOR) is a class of opioid receptors that is critical for analgesia, reward, and euphoria. MOR is distributed in various brain regions, including the hippocampus, where traditionally, it is believed to be localized mainly at the presynaptic terminals of the GABAergic inhibitory interneurons to exert a strong disinhibitory effect on excitatory pyramidal neurons. However, recent intensive research has uncovered the existence of MOR in hippocampal astrocytes, shedding light on how astrocytic MOR participates in opioid signaling via glia-neuron interaction in the hippocampus. Activation of astrocytic MOR has shown to cause glutamate release from hippocampal astrocytes and increase the excitability of presynaptic axon fibers to enhance the release of glutamate at the Schaffer Collateral-CA1 synapses, thereby, intensifying the synaptic strength and plasticity. This novel mechanism involving astrocytic MOR has been shown to participate in hippocampus-dependent conditioned place preference. Furthermore, the signaling of hippocampal MOR, whose action is sexually dimorphic, is engaged in adult neurogenesis, seizure, and stress-induced memory impairment. In this review, we focus on the two profoundly different hippocampal opioid signaling pathways through either GABAergic interneuronal or astrocytic MOR. We further compare and contrast their molecular and cellular mechanisms and their possible roles in opioid-associated conditioned place preference and other hippocampus-dependent behaviors.

μ阿片受体（MOR）是一类对镇痛，奖励和欣快感至关重要的阿片受体。MOR分布在大脑的各个区域，包括海马区，传统上认为MOR主要分布在GABA能抑制性中间神经元的突触前末端，从而对兴奋性锥体神经元产生强大的抑制作用。但是，最近的深入研究发现海马星形胶质细胞中存在MOR，从而阐明了星形胶质MOR如何通过海马中的神经胶质-神经元相互作用参与阿片类信号传导。星形细胞MOR的激活已显示会导致海马星形胶质细胞释放谷氨酸，并增加突触前轴突纤维的兴奋性，从而增强Schaffer Collat​​eral-CA1突触中谷氨酸的释放，因此，增强突触强度和可塑性。这种涉及星形细胞MOR的新机制已显示参与海马依赖性条件性位置偏爱。此外，其作用为性二态的海马MOR信号参与成人神经发生，癫痫发作和应激诱导的记忆障碍。在这篇综述中，我们集中于通过GABA能神经元间或星形细胞MOR的两个完全不同的海马阿片信号通路。我们进一步比较和对比它们的分子和细胞机制，以及它们在与阿片类药物相关的条件性位置偏爱和其他海马依赖性行为中的可能作用。海马MOR的信号是性二态性，它参与成人神经发生，癫痫发作和应激诱导的记忆障碍。在这篇综述中，我们集中于通过GABA能神经元间或星形细胞MOR的两个海马阿片信号通路的截然不同。我们进一步比较和对比他们的分子和细胞机制，以及它们在与阿片类药物相关的条件性位置偏爱和其他海马依赖性行为中的可能作用。海马MOR的信号是性二态性，它参与成人神经发生，癫痫发作和应激诱导的记忆障碍。在这篇综述中，我们集中于通过GABA能神经元间或星形细胞MOR的两个完全不同的海马阿片信号通路。我们进一步比较和对比他们的分子和细胞机制，以及它们在与阿片类药物相关的条件性位置偏爱和其他海马依赖性行为中的可能作用。