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Although no animal model duplicates alcoholism, models for specific factors, like withdrawal, are useful for identifying potential genetic and neural determinants of liability in humans. Previously, we identified a quantitative trait locus (QTL) and gene (<jats:italic>Mpdz<\/jats:italic>, which encodes the multi\u2010PDZ domain protein) on chromosome 4 with a large effect on alcohol withdrawal in mice. Using congenic mice that confirm this QTL and c\u2010Fos expression as a high\u2010resolution marker of neuronal activation, we report that congenic mice show significantly less neuronal activity associated with alcohol withdrawal in the rostroventral caudate putamen (rvCP), but not other parts of the striatum, compared with background strain mice. Moreover, bilateral rvCP lesions significantly increase alcohol withdrawal severity. Using retrograde (fluorogold) and anterograde (Texas Red conjugated dextran amine) tract tracing, we found that \u223c25% of c\u2010Fos immunoreactive rvCP neurons project to caudolateral substantia nigra pars reticulata (clSNr), which we previously found is crucially involved in withdrawal following acute and repeated alcohol exposure. Our results expand upon work suggesting that this QTL impacts alcohol withdrawal via basal ganglia circuitry associated with limbic function, and indicate that an rvCP\u2010clSNr projection plays a critical role. Given the growing body of evidence that the syntenic region of human chromosome 9p and human<jats:italic>MPDZ<\/jats:italic>gene are associated with alcohol abuse, our results may facilitate research on alcohol dependence and associated withdrawal in clinical populations.<\/jats:bold><\/jats:p>","DOI":"10.1111\/j.1601-183x.2010.00611.x","type":"journal-article","created":{"date-parts":[[2010,7,6]],"date-time":"2010-07-06T19:44:58Z","timestamp":1278445498000},"page":"768-776","source":"Crossref","is-referenced-by-count":10,"title":["Rostroventral caudate putamen involvement in ethanol withdrawal is influenced by a chromosome 4 locus"],"prefix":"10.1111","volume":"9","author":[{"given":"G.","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. 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