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

Context associated with morphine withdrawal elicits an increase in serum corticosterone levels. Corticosterone participates in CTR‐MWM by acting on MR, but not GR, in the BLA. MR in BLA→NAcC neurons mediates CTR‐MWM. MR increases presynaptic glutamate release and meanwhile participates in D1 receptor‐induced increases in presynaptic glutamate release and postsynaptic AMPA currents. MR increases the intrinsic excitability of BLA→NAcC neurons during CTR‐MWM. 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→NAcC) 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→NAcC neurons during CTR‐MWM. These results suggest that corticosterone contributes to CTR‐MWM by activating BLA→NAcC neurons through MR pathways, uncovering a link between a systemic hormonal response and a specific CTR‐MWM process. Context associated with morphine withdrawal elicits an increase in serum corticosterone levels. Corticosterone participates in CTR-MWM by acting on MR, but not GR, in the BLA. MR in BLA →NAcC neurons mediates CTR-MWM. MR increases presynaptic glutamate release and meanwhile participates in D1 receptor-induced increases in presynaptic glutamate release and postsynaptic AMPA currents. MR increases the intrinsic excitability of BLA →NAcC neurons during CTR-MWM. 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 →NAcC ) 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 →NAcC neurons during CTR-MWM. These results suggest that corticosterone contributes to CTR-MWM by activating BLA →NAcC neurons through MR pathways, uncovering a link between a systemic hormonal response and a specific CTR-MWM process. Advanced Science, Volume 12, Issue 42, November 13, 2025.