A Series Circuit from CA1 of Dorsal Hippocampus to Basolateral Amygdala via Postrhinal Cortex Participates in Conditioned Context-Induced Retrieval of Morphine Withdrawal Memory

Abstract

Background: Conditioned context-induced retrieval of drug withdrawal memory contributes to drug relapse. The basolateral amygdala (BLA) plays an important role in conditioned context-induced retrieval of morphine withdrawal memory. However, the upstream pathways of the activation of the BLA by conditioned context remains to be studied. Methods: Using the conditioned place aversion model, chemical-genetic method, trans-neuronal virus tracing technique and immunohistochemical method, we studied the upstream neural circuits of the activation of the BLA during conditioned context-induced retrieval of morphine withdrawal memory. Findings: The present results show that the dorsal CA1 of the hippocampus is an upstream brain region of the activation of the BLA during conditioned context-induced withdrawal memory retrieval; the indirect connection from dorsal CA1 of the hippocampus to the BLA is enhanced in mice with conditioned place aversion; the postrhinal cortex (POR) is a brain region that connects the dorsal CA1 of the hippocampus and the activation of the BLA in conditioned context-induced retrieval of morphine withdrawal memory. Interpretation: These results suggest that a series circuit from CA1 of dorsal hippocampus to basolateral amygdala via postrhinal cortex participates in conditioned context-induced retrieval of morphine withdrawal memory. Funding Statement: This study was supported by the National Program of Basic Research sponsored by the Ministry of Science and Technology of China (2009CB52201 and 2013CB835100) and Project of Foundation of National Natural Science of China (31121061, 91332204, 81371466 and 31070932). Declaration of Interests: All authors declare no conflicts of interest. Ethics Approval Statement: All experimental procedures conformed to Fudan University as well as international guidelines on the ethical use of animals. All efforts were made to minimize animal suffering and reduce the number of animals used.