Knockdown and overexpression of basolateral amygdala SIRT1 via AAV bidirectionally alter morphine-induced conditioned place preference extinction in mice
Year: 2025
Type: article
Abstract: Introduction: This study investigates the role of SIRT1 in basolateral amygdala (BLA) glutamatergic neurons in morphine-induced conditioned place preference (CPP). Methods: Via SIRT1 knockdown/overexpression in bilateral BLA of morphine-induced CPP mice. Outcomes measured by behavioral tests, WB, and transmission electron microscopy. Results: 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 anxiety-like 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. Discussion: Our findings reveal that SIRT1 bidirectionally regulates opioid-associated 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.
Authors: Guo Hao, Yao Mingchen, Zheng Yalin, Qu Yaqi, Yang Tingwu, Xing Xinru, Li Kaixuan, Dong Yani, Liu Dongsen
Institution: Beijing Sport University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W4411500868