Corticosterone Contributes to Context-Triggered Retrieval of Morphine Withdrawal Memories by Acting on Basolateral Amygdala Neurons Projecting to Nucleus Accumbens Core.

Adv Sci (Weinh)

State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Center for Brain Science, Department of Neurology of Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Published: August 2025


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Article Abstract

Context-triggered retrieval of drug withdrawal memories (CTR-DWM) is a major cause of drug relapse. Most studies of the context-triggered retrieval of morphine withdrawal memories (CTR-MWM) have mainly focused on the functional interactions within the central structures of the brain. It remains unknown how an increase in corticosterone, which is an important response under drug withdrawal state, participates in CTR-MWM. The present results show that corticosterone contributes to CTR-MWM; within the basolateral amygdala (BLA), it is the mineralocorticoid receptor (MR), rather than the glucocorticoid receptor (GR), activated by corticosterone that mediates CTR-MWM; MR of BLA neurons projecting to the nucleus accumbens core (BLA) mediates CTR-MWM; MR increases presynaptic glutamate release and participates in dopamine D1 receptor -induced increase in presynaptic glutamate release and postsynaptic AMPA (α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid) currents; MR increases intrinsic excitability of BLA neurons during CTR-MWM. These results suggest that corticosterone contributes to CTR-MWM by activating BLA neurons through MR pathways, uncovering a link between a systemic hormonal response and a specific CTR-MWM process.

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http://dx.doi.org/10.1002/advs.202503409DOI Listing

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