{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T14:17:21Z","timestamp":1783520241669,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,5]]},"group-title":"Neuroscience","reference-count":77,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH","award":["R01DA056581 and P30DA013429"],"award-info":[{"award-number":["R01DA056581 and P30DA013429"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  PVT is involved in stress responses, fear, anxiety, arousal, aversion and reward. Anterior and posterior PVT (aPVT and pPVT) have different neuronal connections, molecular contents, and functional roles. PVT expressed a high level of KOR. Herein we mapped the projection targets of aPVT KOR(+) neurons and explored the behavioral significance of aPVT KOR. Using KOR-iCre mice and Cre-dependent anterograde tracer, we found that KOR(+) glutamatergic neurons in aPVT primarily projected to NAc, CeA, BNST, PFC, and reticular nucleus of the thalamus (RT). 3-D images showed the pathway emanating from aPVT to the ventral RT, through NAc, and out to the other regions, indicating widespread axonal collateralization. We conditionally knock-downed KOR (KOR cKD) in aPVT by injection of AAV-eGFP-Cre or AAV-eGFP (control) into aPVT of Oprk1\n                  <jats:sup>lox\/lox<\/jats:sup>\n                  mice. [\n                  <jats:sup>3<\/jats:sup>\n                  H]U69,593 receptor autoradiography revealed substantial KOR cKD in aPVT. In both male and female mice, the KOR cKD in aPVT significantly reduced anxiety-like behaviors in the elevated plus-maze test, cue-induced freezing after fear conditioning and naloxone-precipitated morphine withdrawal-associated jumps. KOR cKD attenuated U50,488H-induced conditioned place aversion in males only, while having no effect on forced swim immobility or the U50,488H-induced visceral analgesic and antipruritic effects in either sex. Thus, our results reveal for the first time that KOR-mediated inhibition of aPVT neurons may mediate morphine withdrawal, anxiety, and cue-induced fear in both sexes but contribute to KOR agonist-induced aversion only in males. Notably, our findings reveal a previously unrecognized role for aPVT in regulating morphine withdrawal, acting in a manner distinct from pPVT.\n                <\/jats:p>","DOI":"10.64898\/2026.06.30.735625","type":"posted-content","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T04:05:11Z","timestamp":1783310711000},"source":"Crossref","is-referenced-by-count":0,"title":["Kappa opioid receptors (KORs) in the anterior paraventricular nucleus of the thalamus (aPVT) mediate morphine withdrawal-, anxiety-, fear-, and KOR agonist-induced aversion-like behaviors in mice"],"prefix":"10.64898","author":[{"given":"Peng","family":"Huang","sequence":"first","affiliation":[{"name":"Center for Substance Abuse Research and Department of Neural Sciences, Temple University Lewis Katz School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongguang","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research and Department of Neural Sciences, Temple University Lewis Katz School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Bland","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research and Department of Neural Sciences, Temple University Lewis Katz School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aryan","family":"Anand","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research and Department of Neural Sciences, Temple University Lewis Katz School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Beier","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research and Department of Neural Sciences, Temple University Lewis Katz School of Medicine, Philadelphia, PA"},{"name":"Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee-Yuan","family":"Liu-Chen","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research and Department of Neural Sciences, Temple University Lewis Katz School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070806251191000_2026.06.30.735625v1.1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0022-3565(25)33422-1","article-title":"U-50,488: a selective and structurally novel non-Mu (kappa) opioid agonist","volume":"224","year":"1983","journal-title":"J. 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