Inputs from paraventricular nucleus of thalamus and locus coeruleus contribute to the activation of central nucleus of amygdala during context-induced retrieval of morphine withdrawal memory

Drug relapse can be mainly ascribed to the retrieval of drug withdrawal memory induced by conditioned context. Previous studies have shown that the central nucleus of the amygdala lateral division (CeL) could be activated by conditioned context. However, what source of input that activates the CeL during conditioned context-induced retrieval of morphine-withdrawal memory remains unknown. In this study, using retrograde labeling, immunohistochemistry, local microinjection and chemogenetic technologies, we found that (1) Conditioned context induced an activation of the CeL and the inhibition of the CeL inhibited the context-induced retrieval of morphine-withdrawal memory; (2) the inhibition of the paraventricular nucleus of thalamus (PVT) or PVT-CeL projection neurons caused an attenuation of the activation of the CeL by conditioned context and conditioned place aversion (CPA); (3) the inhibition of the locus coeruleus (LC) or LC-CeL projection neurons decreased the activation of the CeL by conditioned context and CPA. These results suggest that the CeL is necessary for conditioned context-induced retrieval of morphine-withdrawal memory and inputs from PVT and LC contribute to the activation of the CeL during context-induced retrieval of morphine withdrawal memory.