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A mutant allele (<jats:italic>Taar1<\/jats:italic><jats:sup><jats:italic>m1J<\/jats:italic><\/jats:sup>) derived from the DBA\/2J mouse strain codes for a non\u2010functional receptor, and <jats:italic>Taar1<\/jats:italic><jats:sup><jats:italic>m1J\/m1J<\/jats:italic><\/jats:sup> mice consume more MA than mice possessing the reference <jats:italic>Taar1<\/jats:italic><jats:sup>+<\/jats:sup> allele. To study the impact of this mutation in a genetically diverse population, heterogeneous stock\u2010collaborative cross (HS\u2010CC) mice, the product of an eight\u2010way cross of standard and wild\u2010derived strains, were tested for MA intake. HS\u2010CC had low MA intake, so an HS\u2010CC by DBA\/2J strain F2 intercross was created to transfer the mutant allele onto the diverse background, and used for selective breeding. To study residual variation in MA intake existing in <jats:italic>Taar1<\/jats:italic><jats:sup><jats:italic>m1J\/m1J<\/jats:italic><\/jats:sup> mice, selective breeding for higher (MAH) vs lower (MAL) MA intake was initiated from <jats:italic>Taar1<\/jats:italic><jats:sup><jats:italic>m1J\/m1J<\/jats:italic><\/jats:sup> F2 individuals; a control line of <jats:italic>Taar1<\/jats:italic><jats:sup>+\/+<\/jats:sup> individuals (MAC) was retained. The lines were also examined for MA\u2010induced locomotor and thermal responses, and fluid and tastant consumption. <jats:italic>Taar1<\/jats:italic><jats:sup><jats:italic>m1J\/m1J<\/jats:italic><\/jats:sup> F2 mice consumed significantly more MA than <jats:italic>Taar1<\/jats:italic><jats:sup><jats:italic>+\/+<\/jats:italic><\/jats:sup> F2 mice. Response to selection was significant by generation 2 and there were corresponding differences in fluid consumed. Fluid consumption was not different in non\u2010MA drinking studies. <jats:italic>Taar1<\/jats:italic><jats:sup><jats:italic>m1J\/m1J<\/jats:italic><\/jats:sup> genotype (MAL or MAH vs MAC mice) was associated with heighted MA locomotor and reduced hypothermic responses. MAL mice exhibited greater sensitization than MAH mice, but the selected lines did not consistently differ for thermal or tastant phenotypes. Residual variation among high\u2010risk <jats:italic>Taar1<\/jats:italic><jats:sup><jats:italic>m1J\/m1J<\/jats:italic><\/jats:sup> mice appears to involve mechanisms associated with neuroadaptation to MA, but not sensitivity to hypothermic effects of MA.<\/jats:p>","DOI":"10.1111\/gbb.12667","type":"journal-article","created":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T05:31:04Z","timestamp":1589866264000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A breeding strategy to identify modifiers of high genetic risk for methamphetamine intake"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8798-2347","authenticated-orcid":false,"given":"Cheryl","family":"Reed","sequence":"first","affiliation":[{"name":"Department of Behavioral Neuroscience and Methamphetamine Abuse Research Center Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra M.","family":"Stafford","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience and Methamphetamine Abuse Research Center Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0309-4340","authenticated-orcid":false,"given":"John R. 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