{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:17:48Z","timestamp":1785417468561,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,12]]},"group-title":"Pharmacology and Toxicology","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"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\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30 DA060810"],"award-info":[{"award-number":["P30 DA060810"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Intravenous self-administration (IVSA) of opioids by rats has been shown frequently to exhibit no sex differences, in many cases a higher intake of females, and only rarely higher rates in males. A diversity of methodological parameters (opioid identity, training doses, rat strain, session duration) makes it difficult to identify consistent contributions to these outcomes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To determine if Heterogeneous Stock (HS) rats derived from 8 founder strains differ by sex in the IVSA of opioids.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Male and female Heterogeneous Stock (N=7-8 per sex) rats were permitted to self-administer heroin (20 \u00b5g\/kg\/infusion) in 2 hour sessions under a Fixed Ratio 1 schedule of reinforcement. After acquisition, animals completed sessions in which different infusion doses of heroin (0, 15, 30, 60, 120 \u00b5g\/kg\/infusion), oxycodone (0, 30, 60, 150, 300 \u00b5g\/kg\/infusion) and fentanyl (0, 0.625, 1.25, 2.5, 5.0 \u00b5g\/kg\/infusion) were assessed. Next, animals were evaluated on doses of heroin (15, 30, 60, 120 \u00b5g\/kg\/infusion), oxycodone (30, 60, 150, 300 \u00b5g\/kg\/infusion) and fentanyl (0.625, 1.25, 2.5, 5.0 \u00b5g\/kg\/infusion) under a Progressive Ratio schedule. Anti-nociceptive effects of heroin (0.56-2.4 mg\/kg, s.c.) were examined with a warm water tail-withdrawal assay.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Female HS rats consistently self-administered more infusions of opioids, including heroin during acquisition, all three opioids during FR-1 dose substitution and of oxycodone and fentanyl in the PR procedure. Male rats were moderately more sensitive to the anti-nociceptive effects of heroin.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Female rats drawn at random from a genetically diverse population self-administer opioids at higher rates than their male counterparts.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.08.717349","type":"posted-content","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:25:16Z","timestamp":1776057916000},"source":"Crossref","is-referenced-by-count":2,"title":["Impact of Sex on Heroin Intravenous Self-Administration by Heterogeneous Stock 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":"Sara R. 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