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Pharmacol."],"abstract":"<jats:p>\n                    Stress is a major contributor to the chronic nature of alcohol use disorder (AUD). Orexin (OX) neurons project to the paraventricular nucleus of the thalamus (PVT)\u2014particularly the posterior part (pPVT)\u2014 a structure that plays a key role in stress regulation. The blockade of OX receptors in the pPVT was shown to prevent the stress-induced reinstatement of alcohol seeking in alcohol-dependent rats. Accumulating evidence indicates interactions among OX and dynorphin (DYN) in the pPVT, but unclear is the role of OX and DYN transmission in the pPVT in the stress-induced alcohol seeking during alcohol abstinence. Male Wistar rats were trained to self-administer 10% alcohol for 3\u00a0weeks. They then underwent 6 weeks of chronic intermittent alcohol vapor exposure to induce dependence. After 12 extinction sessions (\u223c3\u00a0weeks of abstinence), the rats received intra-pPVT infusions of the dual OX receptor antagonist TCS1102 (15\u00a0\u00b5g\/0.5\u00a0\u00b5L), the \u03ba-opioid receptor (KOP) antagonist nor-binaltorphimine (norBNI; 4\u00a0\u00b5g\/0.5\u00a0\u00b5L), or their combination, and they were assessed for their reactivity to the stress (footshock)-induced reinstatement of alcohol-seeking behavior. In dependent rats, TCS1102 and norBNI reduced reinstatement but, when co-administered, their individual effects were modulated. At the time of testing, increases in\n                    <jats:italic>Hcrt<\/jats:italic>\n                    and\n                    <jats:italic>Pdyn<\/jats:italic>\n                    mRNA expression in the hypothalamus and a decrease in\n                    <jats:italic>Hcrtr1<\/jats:italic>\n                    expression and an increase in\n                    <jats:italic>Oprk1<\/jats:italic>\n                    expression in the pPVT were observed. These findings reveal a functional interaction among OX receptor and KOP signaling in the pPVT that underlies relapse that is precipitated by stress post-dependence, underscoring the value of multi-target interventions to restore pPVT function and prevent relapse.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2025.1718540","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T06:29:13Z","timestamp":1764224953000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Functional interaction between orexin\/dynorphin transmission in the posterior paraventricular nucleus of the thalamus following alcohol dependence: mediation of alcohol-seeking behavior"],"prefix":"10.3389","volume":"16","author":[{"given":"Francisco J.","family":"Flores-Ramirez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Pascasio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9mi","family":"Martin-Fardon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"347","DOI":"10.2174\/1871527313666140314163920","article-title":"Neuropeptides as therapeutic targets to combat stress-associated behavioral and neuroendocrinological effects","volume":"13","author":"Bali","year":"2014","journal-title":"CNS Neurol. 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