{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T07:05:59Z","timestamp":1792220759661,"version":"4.4.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Alcohol use disorder is a chronic disorder with significant limitations in pharmacological treatments, necessitating the exploration of non-pharmacological interventions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used a model of alcohol self-administration (10% v\/v) to analyze behavioral, neurochemical, and signaling mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings demonstrate that stimulation of the HT7 acupuncture point significantly decreased the frequency of active lever presses in rats self-administering alcohol (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05). Alcohol self-administration increased microglial activity and sigma 1 receptor expression in the habenula (Hb), while HT7 stimulation mitigated these effects, decreasing microglial activity and sigma 1 receptor levels (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05). Additionally, alcohol self-administration reduced brain-derived neurotrophic factor (BDNF) expression in the medial prefrontal cortex (mPFC) and increased tyrosine hydroxylase (TH) levels in the ventral tegmental area (VTA) (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05). HT7 stimulation reversed these alterations by increasing BDNF expression in the mPFC and decreasing TH levels in the VTA (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05). Further investigation revealed that BDNF microinjection into the mPFC inhibited sigma 1 receptor activity in the Hb, while microglial inhibition in the Hb decreased TH expression in the VTA (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05). The administration of the microglial inhibitor MINO to the Hb also reduced alcohol self-administration (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05). <\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These results suggest that HT7 stimulation regulates the mPFC-Hb-VTA circuit, leading to decreased alcohol-seeking behavior. Our study demonstrates that HT7 acupuncture can modulate the mPFC-Hb-VTA circuit, providing a potential non-pharmacological treatment for alcohol-seeking behavior by influencing microglial activity, sigma 1 receptor expression, and TH levels. These findings contribute to a deeper understanding of the neural mechanisms underlying acupuncture\u2019s therapeutic effects on alcohol use disorder.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnbeh.2024.1455622","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T09:37:39Z","timestamp":1730281059000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Mechanical acupuncture at HT7 attenuates alcohol self-administration in rats by modulating neuroinflammation and altering mPFC-habenula-VTA circuit activity"],"prefix":"10.3389","volume":"18","author":[{"given":"Su Yeon","family":"Seo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Kyun","family":"Bang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk Yun","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Jin","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang-Ho","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeonhee","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.bbi.2020.08.002","article-title":"Alcohol use disorder and circulating cytokines: a systematic review and meta-analysis","volume":"89","author":"Adams","year":"2020","journal-title":"Brain Behav. 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Neurol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.conb.2008.09.013","article-title":"Local protein synthesis, actin dynamics, and Ltp consolidation","volume":"18","author":"Bramham","year":"2008","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1097\/00001756-199905140-00010","article-title":"Postsynaptic 5-Ht1A receptors control 5-Ht release in the rat medial prefrontal cortex","volume":"10","author":"Casanovas","year":"1999","journal-title":"Neuroreport"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"eaax1342","DOI":"10.1126\/sciadv.aax1342","article-title":"Acupuncture attenuates alcohol dependence through activation of endorphinergic input to the nucleus accumbens from the arcuate nucleus","volume":"5","author":"Chang","year":"2019","journal-title":"Sci. Adv."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"5359","DOI":"10.1038\/s41598-017-05681-7","article-title":"Spinal pathways involved in somatosensory inhibition of the psychomotor actions of cocaine","volume":"7","author":"Chang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"11540","DOI":"10.1038\/s41598-017-11065-8","article-title":"Molecular mechanisms underlying the involvement of the sigma-1 receptor in methamphetamine-mediated microglial polarization","volume":"7","author":"Chao","year":"2017","journal-title":"Sci. Rep."},{"key":"ref11","first-page":"217","article-title":"Low-dose ethanol excites lateral habenula neurons projecting to Vta, Rmtg, and raphe","volume":"9","author":"Fu","year":"2017","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.pharmthera.2004.06.002","article-title":"The role of mesolimbic dopamine in the development and maintenance of ethanol reinforcement","volume":"103","author":"Gonzales","year":"2004","journal-title":"Pharmacol. Ther."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"6578621","DOI":"10.1155\/2017\/6578621","article-title":"Mechanical stimulation of the Ht7 acupuncture point to reduce ethanol self-administration in rats","volume":"2017","author":"Kang","year":"2017","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.jams.2017.06.006","article-title":"Laser acupuncture at Ht7 improves the cerebellar disorders in valproic acid-rat model of autism","volume":"10","author":"Khongrum","year":"2017","journal-title":"J. Acupunct. Meridian Stud."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1111\/j.1460-9568.2012.08030.x","article-title":"Topography of descending projections from anterior insular and medial prefrontal regions to the lateral habenula of the epithalamus in the rat","volume":"35","author":"Kim","year":"2012","journal-title":"Eur. J. Neurosci."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e81018","DOI":"10.1371\/journal.pone.0081018","article-title":"Peripheral afferent mechanisms underlying acupuncture inhibition of cocaine behavioral effects in rats","volume":"8","author":"Kim","year":"2013","journal-title":"PLoS One"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/npp.2009.110","article-title":"Neurocircuitry of addiction","volume":"35","author":"Koob","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1136\/acupmed-2015-010865","article-title":"Effects of acupuncture at Ht7 on glucose metabolism in a rat model of Alzheimer's disease: an 18F-Fdg-pet study","volume":"34","author":"Lai","year":"2016","journal-title":"Acupunct. Med."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.alcohol.2017.06.002","article-title":"Alcohol intake in two different mouse drinking models after recovery from the lipopolysaccharide-induced sickness reaction","volume":"65","author":"Lainiola","year":"2017","journal-title":"Alcohol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.neulet.2014.05.050","article-title":"Acupuncture at Ht7 suppresses morphine self-administration at high dose through Gaba system","volume":"576","author":"Lee","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/j.neubiorev.2021.04.004","article-title":"Bidirectional role of acupuncture in the treatment of drug addiction","volume":"126","author":"Lee","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1111\/acer.13332","article-title":"Electroacupuncture attenuates hyperalgesia in rats withdrawn from chronic alcohol drinking via habenular mu opioid receptors","volume":"41","author":"Li","year":"2017","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref23","first-page":"20","article-title":"Effect of acupuncture on expression of brain-derived neurotrophic factor gene and protein in frontal cortex and hippocampus of depression rats","volume":"37","author":"Liang","year":"2012","journal-title":"Zhen Ci Yan Jiu"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1136\/acupmed-2015-010773","article-title":"Inhibition of spinal microglia and astrocytes contributes to the anti-allodynic effect of electroacupuncture in neuropathic pain induced by spinal nerve ligation","volume":"34","author":"Liang","year":"2016","journal-title":"Acupunct. Med."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s12576-012-0211-1","article-title":"Acupuncture stimulation at Ht7 alleviates depression-induced behavioral changes via regulation of the serotonin system in the prefrontal cortex of maternally-separated rat pups","volume":"62","author":"Park","year":"2012","journal-title":"J. Physiol. Sci."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.neuroscience.2011.07.013","article-title":"Lateral habenular neurons projecting to reward-processing monoaminergic nuclei express hyperpolarization-activated cyclic nucleotid-gated cation channels","volume":"193","author":"Poller","year":"2011","journal-title":"Neuroscience"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/35049004","article-title":"Neurotrophins as synaptic modulators","volume":"2","author":"Poo","year":"2001","journal-title":"Nat. Rev. Neurosci."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.neuropharm.2016.04.023","article-title":"Involvement of 5-Ht3 receptors in the action of vortioxetine in rat brain: focus on glutamatergic and Gabaergic neurotransmission","volume":"108","author":"Riga","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1097\/ALN.0b013e3181895a83","article-title":"Intrathecal injection of the \u03c21Receptor antagonist Bd1047 blocks both mechanical allodynia and increases in spinal Nr1 expression during the induction phase of rodent neuropathic pain","volume":"109","author":"Roh","year":"2008","journal-title":"J. Am. Soc. Anesthesiol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.neuropharm.2014.08.001","article-title":"Minocycline prevents dynorphin-induced neurotoxicity during neuropathic pain in rats","volume":"86","author":"Rojewska","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1007\/s40263-019-00644-0","article-title":"Outcome assessment in trials of pharmacological treatments for alcohol use disorders: fair and strict testing","volume":"33","author":"R\u00f8sner","year":"2019","journal-title":"CNS Drugs"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"105339","DOI":"10.1016\/j.phrs.2020.105339","article-title":"Sigma-1 receptor: a drug target for the modulation of neuroimmune and neuroglial interactions during chronic pain","volume":"163","author":"Ruiz-Cantero","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1124\/jpet.122.523850","article-title":"Sigma ligand-mediated cytosolic calcium modulation in Bv2 microglia cells","volume":"385","author":"Schober","year":"2023","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"5849","DOI":"10.1038\/s41598-018-23824-2","article-title":"An estradiol-independent Bdnf-Npy cascade is involved in the antidepressant effect of mechanical acupuncture instruments in ovariectomized rats","volume":"8","author":"Seo","year":"2018","journal-title":"Sci. Rep."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"113724","DOI":"10.1016\/j.biopha.2022.113724","article-title":"Electroacupuncture stimulation of Ht7 alleviates sleep disruption following acute caffeine exposure by regulating Bdnf-mediated endoplasmic reticulum stress in the rat medial septum","volume":"155","author":"Seo","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"2348","DOI":"10.3390\/jcm11092348","article-title":"Activation of sigma-1 receptor alleviates Er-associated cell death and microglia activation in traumatically injured mice","volume":"11","author":"Shi","year":"2022","journal-title":"J. Clin. Med."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"3169","DOI":"10.1098\/rstb.2008.0097","article-title":"Cognitive and emotional consequences of binge drinking: role of amygdala and prefrontal cortex","volume":"363","author":"Stephens","year":"2008","journal-title":"Philos. Trans. R Soc. B Biol. Sci."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/j.biopsych.2011.11.010","article-title":"Optogenetic modulation of neural circuits that underlie reward seeking","volume":"71","author":"Stuber","year":"2012","journal-title":"Biol. Psychiatry"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"174","DOI":"10.3389\/fnhum.2014.00174","article-title":"The role of the habenula in drug addiction","volume":"8","author":"Velasquez","year":"2014","journal-title":"Front. Hum. Neurosci."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"e0243857","DOI":"10.1371\/journal.pone.0243857","article-title":"Network preservation reveals shared and unique biological processes associated with chronic alcohol abuse in Nac and Pfc","volume":"15","author":"Vornholt","year":"2020","journal-title":"PLoS One"},{"key":"ref41","volume-title":"Harmful use of alcohol, alcohol dependence and mental health conditions: a review of the evidence for their association and integrated treatment approaches","year":"2019"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1111\/j.1530-0277.2010.01310.x","article-title":"Acupuncture inhibits Gaba neuron activity in the ventral tegmental area and reduces ethanol self-administration","volume":"34","author":"Yang","year":"2010","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"e12649","DOI":"10.1111\/gbb.12649","article-title":"Antidepressant mechanism of classical herbal formula lily bulb and Rehmannia decoction: insights from gene expression profile of medial prefrontal cortex of mice with stress-induced depression-like behavior","volume":"19","author":"Zhang","year":"2020","journal-title":"Genes Brain Behav."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.neulet.2014.03.018","article-title":"Involvement of amygdaloid neuropeptide Y in the anxiolytic effects of acupuncture during ethanol withdrawal in rats","volume":"567","author":"Zhao","year":"2014","journal-title":"Neurosci. 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