Acupuncture improves depressive-like behaviors in CUMS rats by modulating lateral habenula synaptic plasticity via the BDNF/ERK/mTOR pathway

Acupuncture has been found to alleviate depressive behaviors caused by chronic unpredictable mild stress (CUMS) in rats. This study explores how acupuncture improves depressive behaviors by modulating synaptic plasticity in the lateral habenula through stimulation of Fengfu and Shangxing acupoints. Male Sprague-Dawley rats were divided into six groups, with the control group excluded. Undergoing a 28-day CUMS protocol, the intervention groups included sham needle stimulation, daily stimulation at the Fengfu (GV16) and Shangxing (GV23) acupoints on alternate days, fluoxetine (2.1 mg/kg, 0.21 mg/mL), or electroacupuncture treatment. All rats were weighed and subjected to behavioral tests. Western blotting was used to examine the expression of the BDNF/ERK/mTOR signaling pathway and associated proteins in the lateral habenula. The monoamine neurotransmitters in serum were measured using ELISA kits. Immunofluorescence staining was used to determine the expression levels of BDNF, TrkB, SYP, and PSD95 in the lateral habenula. Golgi staining was employed to quantify dendritic spine morphology. The study showed that CUMS led to depressive-like behaviors and downregulated the BDNF/ERK/mTOR signaling pathway in the lateral habenula. It also resulted in reduced expression of monoamine neurotransmitters in peripheral blood and changes in dendritic spine length and density. Importantly, both fluoxetine and acupuncture had varying degrees of preventive and restorative effects on these changes. The findings of this study suggest that acupuncture has the potential to activate the BDNF/ERK/mTOR signaling pathway in the lateral habenula of CUMS rats, thereby enhancing synaptic plasticity and exerting an antidepressant effect.