Abstract
The Shenmen point (acupuncture point heart 7: HT7), located in the heart meridian, is frequently used to treat mental disorders, including drug addiction, anxiety, and depression. This study aimed to determine how HT7 regulates anxiety and negative emotions caused by repeated alcohol administration, focusing on the amygdala and paraventricular nucleus (PVN). Repeated administration of alcohol (ETOH; 2 g/kg, i.p. injection, 16% v/v) for 14 days increased the corticosterone (CORT) levels, and HT7 stimulation reduced the plasma CORT levels. HT7 stimulation mitigated anxiety-like behaviors and reduced 22-kHz ultrasonic vocalizations in rats receiving repeated ETOH injections. HT7 stimulation increased the amygdala expression of mature brain-derived neurotropic factor (mBDNF) and phosphorylated tropomyosin receptor kinase B (pTrkB) and decreased the PVN corticotropin-releasing hormone (CRH) expression. Amygdala microinjections of the TrkB antagonist ANA-12 (0.1 pmol/1 μL) reversed the increase in PVN CRH levels. The reduced PVN CRH levels were regulated by CRH-expressing neurons in the amygdala, and the increased amygdala CRH levels were affected by the HT7-stimulation induced increases in mBDNF. HT7 stimulation alleviates increased stress hormone levels and mitigates anxiety and negative emotions caused by repeated ETOH administration. These results provide scientific support for the clinical use of acupuncture to treat various alcoholism-induced diseases.
Highlights
According to the statistics from the world health organization, approximately 283 million people have alcohol use disorders
We previously showed that use of the mechanical acupuncture instrument (MAI) at the HT7 point effectively reduces alcohol consumption in rats [21] and that its stimulation regulates immobility and 22-kHz ultrasonic vocalizations (USVs) via σ 1 R in the ventral tegmental area (VTA) upon acute alcohol exposure [22]
Based on the confirmation of the connection between the amygdala and paraventricular nucleus (PVN) mediated by corticotropin-releasing hormone (CRH)-expressing neurons, we identified a relationship between brain-derived neurotrophic factor (BDNF) expression in the amygdala and CRH expression in the PVN
Summary
According to the statistics from the world health organization, approximately 283 million people have alcohol use disorders. The HPA axis, which is one of the major stress response pathways, has been actively studied in animal models of alcoholism based on the binge/heavy drinking-induced activation of brain stress systems and the chronic relapsing nature of alcohol use disorders [7]. Animal and human studies have demonstrated that an acute alcohol challenge enhances the activity of the HPA axis and pituitary β-endorphin [8]. In contrast to the effects of an acute alcohol challenge, animal studies have demonstrated that chronic alcohol consumption decreases the hypothalamic proopiomelanocortin messenger RNA (mRNA) expression [9]. Activation of the HPA axis following alcohol administration exerts various effects, such as the induction of stress- and addiction-related behaviors [10]. Increased alcohol consumption induces a negative feedback phenomenon that activates brain stress systems and increases stress hormone levels
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