{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:35:40Z","timestamp":1785429340885,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,10]]},"group-title":"Pharmacology and Toxicology","reference-count":38,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01 DA057423"],"award-info":[{"award-number":["R01 DA057423"]}],"id":[{"id":"https:\/\/ror.org\/00fq5cm18","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Evidence suggests steeper accelerating opioid-related overdose, and non-medical use rates, in middle aged men in recent years compared with younger cohorts. Little is known about whether this is driven by age-related differences in the effects of opioids compared with socio-cultural factors driving non-medical consumption. Rodent models can be useful for dissociating biological from psychosocial factors, however, only minimal evidence exists on the effects of opioids in middle-age rats.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To determine if the anti-nociceptive and rewarding effects of opioids differ between adult and middle-age rats.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Female and male Wistar rats were obtained in early adulthood and examined across 4 to 11 months of age for nociceptive responses to heroin (0-1.56 mg\/kg, s.c.) using a warm-water tail withdrawal assay. Subgroups (N=8 per group) were initiated on intravenous self-administration (IVSA) of heroin at either 5 months or 12 months of age.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Anti-nociceptive effects of heroin did not differ across age. Female rats that initiated IVSA in early adulthood or middle-age obtained significantly more infusions of heroin than male rats of the same age during acquisition, and in dose-substitution under a FR1 schedule. Male, but not female, rats that initiated IVSA in middle age self-administered less heroin then rats that initiated in early adulthood; this was observed in acquisition and in dose-substitution.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>This study shows that opioid reward is diminished in middle aged male rats. It also found that middle age rats can be used effectively to model opioid-related outcomes, including drug seeking using the IVSA procedure.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.05.723054","type":"posted-content","created":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T11:40:12Z","timestamp":1778413212000},"source":"Crossref","is-referenced-by-count":1,"title":["Impact of Age on Heroin Intravenous Self-Administration in Wistar Rats"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9827-1738","authenticated-orcid":false,"given":"Michael A.","family":"Taffe","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego; La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney L.","family":"Mehl","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego; La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanabel","family":"Grant","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego; La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia A.","family":"Vandewater","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego; La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026051215400673000_2026.05.05.723054v1.1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-014-3819-4"},{"key":"2026051215400673000_2026.05.05.723054v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(99)00133-5"},{"key":"2026051215400673000_2026.05.05.723054v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.09.020"},{"key":"2026051215400673000_2026.05.05.723054v1.4","doi-asserted-by":"publisher","DOI":"10.1037\/\/1064-1297.9.3.307"},{"key":"2026051215400673000_2026.05.05.723054v1.5","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.784365"},{"key":"2026051215400673000_2026.05.05.723054v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(02)01039-0"},{"key":"2026051215400673000_2026.05.05.723054v1.7","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15791"},{"key":"2026051215400673000_2026.05.05.723054v1.8","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-025-06920-w"},{"key":"2026051215400673000_2026.05.05.723054v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2008.11.012"},{"key":"2026051215400673000_2026.05.05.723054v1.10","unstructured":"Garber, J.C. , Barbee, R.W. , Bielitzki, J.T. , Clayton, L.A. , Donovan, J.C. , Hendriksen, C.F.M. , Kohn, D.F. , Lipman, N.S. , Locke, P.A. , Melcher, J. , Quimby, F.W. , Turner, P.V. , Wood, G.A. , Wurbel, H. , 2011. 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