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Neurochem.<\/jats:italic> (2012) <jats:bold>121<\/jats:bold>, 373\u2013382.<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Several metabolic neuroimaging studies have indicated that bipolar patients with mania exhibit alterations in metabolic activity, suggesting that perturbations in corticolimbic function contribute to the functional deficits associated with the disease. Because pharmacological stimulation of K<jats:sub>v<\/jats:sub>7 channel function has shown anti\u2010manic like efficacy in the D\u2010amphetamine and chlordiazepoxide (AMPH+CDP) induced hyperactivity mouse model of mania, we addressed whether this effect of K<jats:sub>v<\/jats:sub>7 channels could be associated with changes in cerebral [<jats:sup>14<\/jats:sup>C]2\u2010deoxyglucose (2\u2010DG) uptake, a surrogate marker of brain metabolic activity. Acute administration of the Kv7 channel modulators, retigabine (pan K<jats:sub>v<\/jats:sub>7.2\u2010K<jats:sub>v<\/jats:sub>7.5 channel opener) and ICA\u201027243 (K<jats:sub>v<\/jats:sub>7.2\/K<jats:sub>v<\/jats:sub>7.3 channel\u2010preferring opener) reduced 2\u2010DG uptake in several mouse forebrain structures with a brain regional signature similar to the mood stabilizers, lithium and valproate. Combined administration of AMPH+CDP enhanced 2\u2010DG uptake in the striatum, cortex and thalamus, and both retigabine and ICA\u201027243 fully prevented this stimulatory effect of AMPH+CDP. In addition, both K<jats:sub>v<\/jats:sub>7 channel openers dose\u2010dependently increased phospho\u2010serine\u20109 levels of GSK3\u03b2 in the prefrontal cortex and hippocampus, a common molecular mechanism shared by anti\u2010manic drugs. In combination, these data emphasize the potential of K<jats:sub>v<\/jats:sub>7 channel openers in the treatment of bipolar disorder, and suggest that heteromeric K<jats:sub>v<\/jats:sub>7.2\/K<jats:sub>v<\/jats:sub>7.3 channels may present a novel anti\u2010manic therapeutic target.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1471-4159.2012.07704.x","type":"journal-article","created":{"date-parts":[[2012,2,22]],"date-time":"2012-02-22T19:45:21Z","timestamp":1329939921000},"page":"373-382","source":"Crossref","is-referenced-by-count":18,"title":["K<sub>v<\/sub>7 (KCNQ) channel openers normalize central 2\u2010deoxyglucose uptake in a mouse model of mania and increase prefrontal cortical and hippocampal serine\u20109 phosphorylation levels of GSK3\u03b2"],"prefix":"10.1111","volume":"121","author":[{"given":"Line 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