Extracellular signal-regulated kinase in the basolateral amygdala is required for reconsolidation of heroin-associated memory

Abstract

Reconsolidation of heroin-associated memory is an independent memory process that occurs following retrieval, which is essential for the sustained capacity of an associative drug stimulus to precipitate heroin-seeking. Extracellular signal-regulated kinase (ERK) in the basolateral amygdala (BLA) mediates the reconsolidation of drug memory. In the present study, we utilized a rat model of drug craving and relapse to verify the hypothesis that the reconsolidation of heroin-associated memory requires ERK in an instrumental heroin-seeking behavior, focusing on the BLA brain region, which is crucial for synaptic plasticity and memory processes. We found that bilateral intra-BLA infusions of U0126 (1 μg/0.5 μl), an ERK inhibitor, immediately after retrieving heroin-associated memory significantly reduced cue-induced and drug-induced reinstatement and spontaneous recovery of heroin-seeking compared to the vehicle. Furthermore, this inhibitory effect was related to the characteristic of reconsolidation. Conversely, no effect was observed on the heroin-seeking behavior when the intra-BLA infusion of U0126 was administered 6 h after the heroin-associated memory retrieval or without memory retrieval. Together, these data suggest that disrupting the reconsolidation of heroin-associated memory via an ERK inhibitor may serve as a promising option for treating relapse in opiate addicts.

Activation of Epac in the BLA disrupts reconsolidation and attenuates heroin‐seeking behaviour

“…Pharmacological interventions targeting the BLA during memory reactivation or immediately thereafter have shown promising results in preventing the reinstatement of drug‐seeking behaviour. These interventions include the use of DNA methyltransferase inhibitors (such as 5‐AZA), 21,22 histone deacetylase inhibitors (such as TSA), 23 NMDA receptor antagonists (such as MK801 and D‐APV), 24,25 β‐adrenergic receptor antagonists (such as propranolol) 26,27 and extracellular signal‐regulated kinase inhibitors (such as U0126) 28,29 . These findings underscore the pivotal involvement of the BLA in the reconsolidation of memories associated with drug use.…”

Targeting Abnormal Tau Phosphorylation for Alzheimer’s Therapeutics

“…The resultant hyperactivation and mislocalization of CDK5 lead to the hyperphosphorylation of its substrates. CDK5 phosphorylates Tau, which is a crucial substrate of CDK5, and causes it to disassociate from microtubules, self-aggregate, and eventually form PHFs and insoluble NFTs in neurons 61 62 63 64 65 .…”