Effects of Acupuncture on Chronic Stress-Induced Depression-Like Behavior and Its Central Neural Mechanism

Depression is a serious psychiatric condition affecting about 10% of the world's population and representing a significant socioeconomic burden. This condition is frequently associated with chronic pain, fatigue, inflammatory diseases, and other health complications. Although traditional antidepressants, such as selective serotonin reuptake inhibitors, are widely used, many patients do not respond adequately or experience problematic side effects. In this context, alternative therapies such as acupuncture have attracted scientific attention for their promising effects in the treatment of depression, with rare adverse events reported.

This study investigated the effects of a specific combination of acupuncture points in the treatment of depressive behaviors induced by chronic stress in animal models. The researchers used male mice subjected to chronic restraint stress for 14 or 28 consecutive days to induce depression-like behaviors. The animals were then treated with acupuncture using different point combinations: the main combination studied included the points KI-10, LR-8, LU-8, and LR-4, while control groups received treatment at different points or at sites unrelated to acupuncture. This specific point combination is widely used in traditional Korean medicine, following the Sa-am acupuncture method, especially for treating pain conditions and psychological disorders such as depression.

To assess depressive behaviors, the researchers used the open field test, which measures the locomotor and exploratory activity of the animals. Depressed mice typically show reduced movement and exploration. The study also analyzed neuronal activity in the brain in detail through expression of the c-Fos protein, a marker of neuronal activity, in 30 different brain regions. In addition, the researchers investigated how the treatment affected serotonin receptors, specifically the 5-HT1A and 5-HT1B subtypes, which are central to the mechanisms of depression.

The results showed that acupuncture treatment with the combination of KI-10, LR-8, LU-8, and LR-4 was effective in reversing the depressive behaviors induced by stress. Treated animals showed significant improvements in total distance traveled and in the number of zone transitions in the behavioral test, indicating a reduction in depressive symptoms. Interestingly, when the researchers tested only the points KI-10 and LR-8, the therapeutic effects were similar, suggesting that these two points are the main contributors to the benefits observed. In contrast, treatment with control points or at sites unrelated to acupuncture did not produce behavioral improvements.

The analysis of neuronal activity revealed that the specific treatment activated brain regions important for emotional and motor processing, including the hippocampus, cingulate cortex, motor cortex, insular cortex, thalamus, and hypothalamus. These areas are known to be altered in depression and to participate in the regulation of mood and stress. The study also showed that acupuncture treatment increased the expression of 5-HT1A serotonin receptors in the cortex, hippocampus, thalamus, and hypothalamus, and of 5-HT1B receptors in the cortex and thalamus. This finding is particularly relevant because the serotonergic system is considered central to the mechanisms of depression, and many conventional antidepressants target precisely this system.

For patients suffering from depression, these results offer promising scientific evidence on how acupuncture may function as a complementary or alternative treatment. The study suggests that acupuncture does not merely produce placebo effects but activates specific neurobiological mechanisms that may help in recovery from depression. For health professionals, the research provides valuable insights into which acupuncture points may be most effective and how this therapy can be integrated into the conventional treatment of depression. The identification that KI-10 and LR-8 are particularly important may guide more focused and efficient treatment protocols.

It is important to recognize the limitations of this study. The research was carried out in animal models, and although it provides valuable information about biological mechanisms, the results need to be validated in clinical studies with humans. The restraint stress model used may not fully capture the complexity of human depression, which involves diverse genetic, social, psychological, and environmental factors. In addition, the study focused on specific aspects of the serotonergic system, but depression involves multiple neurotransmitter systems that warrant further investigation.

Future research should explore other molecular markers such as CREB, ERK, and BDNF to better understand the mechanisms of action of acupuncture. Despite these limitations, this work represents a significant advance in the scientific understanding of how acupuncture may help in the treatment of depression, offering hope to millions of people seeking effective and safe therapeutic alternatives.