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The GIRK2 subunit is thought to play key roles in the reward system. <jats:italic>Weaver<\/jats:italic> mutant mice exhibit abnormal GIRK2 function and different behaviors that are caused by several addictive substances compared with wild\u2010type mice. However, mechanisms of reward\u2010related alterations in <jats:italic>weaver<\/jats:italic> mutant mice remain unclear. The present study investigated changes in the rewarding effects of methamphetamine (METH) in <jats:italic>weaver<\/jats:italic> mutant mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The rewarding effects of METH (4.0\u00a0mg\/kg) were investigated using the conditioned place preference (CPP) paradigm. Extracellular dopamine level in the nucleus accumbens (NAc) was measured by in vivo microdialysis. To identify brain regions that were associated with these changes in rewarding effects, METH\u2010induced alterations of Fos expression were investigated by immunohistochemical analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Weaver<\/jats:italic> mutant mice exhibited a significant decrease in METH\u2010induced CPP and dopamine release in the NAc. Methamphetamine significantly increased Fos expression in the posterior NAc (pNAc) shell in wild\u2010type but not in <jats:italic>weaver<\/jats:italic> mutant mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Methamphetamine did not induce rewarding effects in <jats:italic>weaver<\/jats:italic> mutant mice. The pNAc shell exhibited a significant difference in neuronal activity between wild\u2010type and <jats:italic>weaver<\/jats:italic> mutant mice. The present results suggest that the absence of METH\u2010induced CPP in <jats:italic>weaver<\/jats:italic> mutant mice is probably related to an innate reduction of dopamine and decreased neural activity in the pNAc shell that is partially attributable to the change of GIRK channel function. GIRK channels, especially those containing the GIRK2 subunit, appear to be involved in METH dependence.<\/jats:p><\/jats:sec>","DOI":"10.1002\/npr2.12130","type":"journal-article","created":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T10:32:13Z","timestamp":1597833133000},"page":"324-331","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Absence of methamphetamine\u2010induced conditioned place preference in <i>weaver<\/i> mutant mice"],"prefix":"10.1002","volume":"40","author":[{"given":"Yuiko","family":"Ikekubo","sequence":"first","affiliation":[{"name":"Addictive Substance Project Tokyo Metropolitan Institute of Medical Science  Tokyo Japan"},{"name":"Molecular and Cellular Medicine Graduate School of Medical and Dental Sciences Niigata University  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soichiro","family":"Ide","sequence":"additional","affiliation":[{"name":"Addictive 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