ORIGINAL RESEARCH article
Front. Cell. Neurosci.
Sec. Cellular Neuropathology
Volume 19 - 2025 | doi: 10.3389/fncel.2025.1604914
This article is part of the Research TopicNovel Approaches to Foster Brain Plasticity in Neurodevelopmental and Neurodegenerative DisordersView all articles
Knockdown and Overexpression of Basolateral Amygdala SIRT1 via AAV Bidirectionally Alter Morphine-Induced Conditioned Place Preference Extinction in Mice
Provisionally accepted
- Beijing Sport University, Beijing, China
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This study investigates the role of SIRT1 in basolateral amygdala (BLA) glutamatergic neurons in morphine-induced conditioned place preference (CPP). Using specific SIRT1 knockdown or overexpression, we found that SIRT1 knockdown prolonged CPP extinction and enhanced reinstatement, whereas overexpression accelerated extinction and attenuated relapse. Behavioral tests revealed that SIRT1 knockdown rescued morphine-induced memory impairment and anxietylike behaviors, while overexpression exacerbated these effects. Ultrastructural and molecular analyses demonstrated SIRT1 modulation of synaptic plasticity-related proteins (BDNF, PSD95) and synaptic ultrastructure in BLA. Our findings reveal that SIRT1 bidirectionally regulates opioidassociated memory persistence through synaptic remodeling, highlighting its potential as an epigenetic target for addiction treatment. While SIRT1 is implicated in neuroplasticity, its specific role in modulating opioid-associated memory circuits within the BLA remains undefined, representing a critical gap in understanding addiction neuropathology.
Keywords: SIRT1, basolateral amygdala, Morphine, conditioned place preference, extinction, reinstatement, BDNF, psd95
Received: 02 Apr 2025; Accepted: 22 May 2025.
Copyright: © 2025 Hao, Mingchen, Yalin, Yaqi, Tingwu, xingru, Kaixuan, Yani and Dongsen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Liu Dongsen, Beijing Sport University, Beijing, China
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