Crucial role of feedback signals from prelimbic cortex to basolateral amygdala in the retrieval of morphine withdrawal memory

An important reasons for drug relapse is the retrieval of drug withdrawal memory induced by conditioned context. Previous studies have suggested that the basolateral amygdala (BLA) plays an important role in conditioned context–induced retrieval of morphine withdrawal memory. However, the downstream neuronal circuits of the activation of the BLA in conditioned context–induced retrieval of morphine withdrawal memory remain unknown. Using retrograde labeling, immunohistochemical, and optogenetic approaches, we found that, although BLA neurons projecting to the prelimbic cortex (PrL) played an important role in conditioned context–induced retrieval of morphine withdrawal memory, they do not exhibit increased expression of the neuronal plasticity marker Arc. However, when PrL neurons activated by the BLA send feedback signals to the BLA, a neuronal-related process is induced in other BLA neurons that do not project to the PrL, a finding that is relevant to conditioned context–induced retrieval of morphine withdrawal memory.