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Methylphenidate, a psychostimulant that causes dopamine overflow (among other effects), alters gene regulation in neurons of the striatum. The present study compared the effects of acute and repeated methylphenidate treatment on cortical and striatal gene regulation in adolescent rats. Changes in the expression of the immediate\u2013early genes <jats:italic>zif\u2003268<\/jats:italic> and <jats:italic>homer\u20031a<\/jats:italic> were mapped in 23 striatal sectors and 22 cortical areas that provide input to these striatal sectors, in order to determine whether specific corticostriatal circuits were affected by these treatments. Acute administration of methylphenidate (5\u2003mg\/kg, i.p.) produced modest <jats:italic>zif\u2003268<\/jats:italic> induction in cortical areas. These cortical <jats:italic>zif\u2003268<\/jats:italic> responses were correlated in magnitude with <jats:italic>zif\u2003268<\/jats:italic> induction in functionally related striatal sectors. In contrast, after repeated methylphenidate treatment (10\u2003mg\/kg, 7\u2003days), cortical and striatal gene induction were dissociated. In these animals, the methylphenidate challenge (5\u2003mg\/kg) produced significantly greater gene induction (<jats:italic>zif\u2003268<\/jats:italic> and <jats:italic>homer\u20031a<\/jats:italic>) in the cortex. This enhanced response was widespread but regionally selective, as it occurred predominantly in premotor, motor and somatosensory cortical areas. At the same time, striatal gene induction was partly suppressed (<jats:italic>zif\u2003268<\/jats:italic>) or unchanged (<jats:italic>homer\u20031a<\/jats:italic>). Thus, repeated methylphenidate treatment disrupted the normally coordinated gene activation patterns in cortical and striatal nodes of corticostriatal circuits. This drug\u2010induced dissociation in cortical and striatal functioning was associated with enhanced levels of behavioural stereotypies, suggesting disrupted motor switching function.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2007.05570.x","type":"journal-article","created":{"date-parts":[[2007,6,28]],"date-time":"2007-06-28T11:05:53Z","timestamp":1183028753000},"page":"3617-3628","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Dysregulation of gene induction in corticostriatal circuits after repeated methylphenidate treatment in adolescent rats: differential effects on <i>zif\u2003268<\/i> and <i>homer\u20031a<\/i>"],"prefix":"10.1111","volume":"25","author":[{"given":"Lindsay","family":"Cotterly","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel A.","family":"Beverley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoyo","family":"Yano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Steiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,6,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300962"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(89)90074-X"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)62678-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.09.030186.002041"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.1091"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300818"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-24-10579.1998"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(99)00041-8"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90884-P"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903160305"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)81056-9"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-14-05301.1998"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-12-04752.1997"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1992.68.3.767"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(01)00757-2"},{"key":"e_1_2_7_17_1","first-page":"496","article-title":"Activation of transcription factor genes in striatum by cocaine: role of both serotonin and dopamine systems","volume":"267","author":"Bhat R.V.","year":"1993","journal-title":"J. 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