# Knockdown and overexpression of basolateral amygdala SIRT1 via AAV bidirectionally alter morphine-induced conditioned place preference extinction in mice

## TL;DR

This study shows that changing SIRT1 levels in mice brains affects how quickly they forget a morphine-related memory, which could help treat addiction.

## Contribution

The study reveals that SIRT1 in the basolateral amygdala bidirectionally regulates opioid memory extinction and synaptic plasticity.

## Key findings

- SIRT1 knockdown prolonged CPP extinction and enhanced reinstatement, while overexpression accelerated extinction and reduced relapse.
- SIRT1 modulation affected synaptic plasticity-related proteins (BDNF, PSD95) and synaptic ultrastructure in the BLA.
- Behavioral tests showed SIRT1 knockdown rescued morphine-induced memory impairment and anxiety, while overexpression worsened these effects.

## Abstract

This study investigates the role of SIRT1 in basolateral amygdala (BLA) glutamatergic neurons in morphine-induced conditioned place preference (CPP).

Via SIRT1 knockdown/overexpression in bilateral BLA of morphine-induced CPP mice. Outcomes measured by behavioral tests, WB, and transmission electron microscopy.

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.

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.