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Cue\u2010evoked drug craving progressively increases and contributes to perpetual relapse. Preclinical models have determined that glutamate receptor plasticity within the nucleus accumbens (NAc) drives amplified cue\u2010evoked drug seeking after prolonged abstinence (&gt;40\u2009days). Isolated condition (IC) rearing increases cocaine and amphetamine (AMP) self\u2010administration and cue\u2010induced reinstatement. We tested the hypothesis that housing in the IC will augment AMP seeking after short and prolonged abstinence from AMP self\u2010administration when compared with rats reared in the enrichment condition (EC). EC and IC male rats acquired stable AMP or SAL self\u2010administration and were tested in a cue\u2010induced AMP\u2010seeking test after 1 and 40\u2009days of abstinence. After the seeking test, the whole NAc was extracted and prepared for western blot analysis. Results indicate that IC rats had more active lever presses during a brief extinction interval and during the cue\u2010induced seeking test. After 40\u2009days of abstinence, IC rats had more active lever presses than EC rats during the cue\u2010induced seeking test. Western blots indicated that the expression ratio between GluA1:mGlur5 was reduced only in IC\u2010AMP\u2010trained rats and the ratio between GluA1:mGlur1 was positively correlated with AMP seeking after prolonged abstinence in IC\u2010AMP rats. These results indicate that IC housing engenders a vulnerable phenotype prone to persistent AMP seeking. The behavioural momentum of this vulnerable phenotype is further revealed when AMP\u2010associated cues are presented following prolonged abstinence.<\/jats:p>","DOI":"10.1111\/ejn.15441","type":"journal-article","created":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T18:13:55Z","timestamp":1630779235000},"page":"6382-6396","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Isolation housing elevates amphetamine seeking independent of nucleus accumbens glutamate receptor adaptations"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4760-7048","authenticated-orcid":false,"given":"Erik J.","family":"Garcia","sequence":"first","affiliation":[{"name":"Department of Psychological Sciences Kansas State University  Manhattan Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2165-990X","authenticated-orcid":false,"given":"Mary E.","family":"Cain","sequence":"additional","affiliation":[{"name":"Department of Psychological Sciences Kansas State University  Manhattan Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2010.07114.x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12386"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-934-5_10"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2656-12.2013"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2013.131"},{"key":"e_1_2_11_7_1","volume-title":"Differential rearing alters amphetamine self\u2010administration: Role of mGluR2\/3 activation","author":"Arndt D. 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