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Rat genome\u2010wide microarrays containing &gt;24\u2009000 probesets were used to examine separate and co\u2010occurring effects of <jats:styled-content style=\"fixed-case\">NVHLs<\/jats:styled-content> and cocaine sensitization (15\u2009mg\/kg\/day\u2009\u00d7\u20095\u2009days) on gene expression within medial prefrontal cortex (<jats:styled-content style=\"fixed-case\">MPFC<\/jats:styled-content>), nucleus accumbens (<jats:styled-content style=\"fixed-case\">NAC<\/jats:styled-content>), and caudate\u2010putamen (<jats:styled-content style=\"fixed-case\">CAPU<\/jats:styled-content>). Two weeks after <jats:styled-content style=\"fixed-case\">NVHLs<\/jats:styled-content> robustly amplified cocaine behavioral sensitization, brains were harvested for genes of interest defined as those altered at <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001 by <jats:styled-content style=\"fixed-case\">NVHL<\/jats:styled-content> or cocaine effects or interactions. Among 135 genes so impacted, <jats:styled-content style=\"fixed-case\">NVHLs<\/jats:styled-content> altered twofold more than cocaine, with half of all changes in the <jats:styled-content style=\"fixed-case\">NAC<\/jats:styled-content>. Although no genes were changed in the same direction by both <jats:styled-content style=\"fixed-case\">NVHL<\/jats:styled-content> and cocaine history, the anatomy and directionality of significant changes suggested synergy on the neural circuit level generative of compounded behavioral phenotypes: <jats:styled-content style=\"fixed-case\">NVHL<\/jats:styled-content> predominantly downregulated expression in <jats:styled-content style=\"fixed-case\">MPFC<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">NAC<\/jats:styled-content> while <jats:styled-content style=\"fixed-case\">NVHL<\/jats:styled-content> and cocaine history mostly upregulated <jats:styled-content style=\"fixed-case\">CAPU<\/jats:styled-content> expression. From 75 named genes altered by <jats:styled-content style=\"fixed-case\">NVHL<\/jats:styled-content> or cocaine, 27 had expression levels that correlated significantly with degree of behavioral sensitization, including 11 downregulated by <jats:styled-content style=\"fixed-case\">NVHL<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">MPFC<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">NAC<\/jats:styled-content>, and 10 upregulated by <jats:styled-content style=\"fixed-case\">NVHL<\/jats:styled-content> or cocaine in <jats:styled-content style=\"fixed-case\">CAPU<\/jats:styled-content>. These findings suggest that structural and functional impoverishment of prefrontal\u2010cortical\u2010accumbens circuits in mental illness is associated with abnormal striatal plasticity compounding with that in addictive disease. Polygenetic interactions impacting neuronal signaling and morphology within these networks likely contribute to addiction vulnerability in mental illness<\/jats:bold>.<\/jats:p>","DOI":"10.1111\/gbb.12051","type":"journal-article","created":{"date-parts":[[2013,5,17]],"date-time":"2013-05-17T18:07:03Z","timestamp":1368814023000},"page":"564-575","source":"Crossref","is-referenced-by-count":23,"title":["Cortical\u2013striatal gene expression in neonatal hippocampal lesion (NVHL)\u2010amplified cocaine sensitization"],"prefix":"10.1111","volume":"12","author":[{"given":"R. A.","family":"Chambers","sequence":"first","affiliation":[{"name":"Lab for Translational Neuroscience of Dual Diagnosis &amp; Development, Department of Psychiatry, Institute for Psychiatric Research Indiana University School of Medicine Indianapolis IN 46202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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