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Rats (30\u2010 to 44\u2010days old) were administered MPH (2 mg\/kg, i.p once daily) or saline (SAL). At the end of the treatment we collected plasma, testicular, liver, and brain (striatum) samples. The testes and liver were used to evaluate conventional reproductive and metabolic endpoints. Testes of MPH\u2010exposed rats weighed more and contained an increased quantity of sperm, whereas testicular levels of testosterone (TST) were markedly decreased. The MPH treatment exerted an inductive effect on enzymatic activity of TST hydroxylases, resulting in increased hepatic TST catabolism. These findings suggest that subchronic MPH exposure in adolescent rats could have a trophic action on testis growth and a negative impact on TST metabolism. We have analyzed striatal gene expression profiles as a consequence of MPH exposure during adolescence, using microarray technology. More than 700 genes were upregulated in the striatum of MPH\u2010treated rats (foldchange &gt;1.5). A first group of genes were apparently involved in migration of immature neural\/glial cells and\/or growth of novel axons. These genes include matrix proteases (ADAM\u20101, MMP14), their inhibitors (TIMP\u20102, TIMP\u20103), the hyaluronan\u2010mediated motility receptor (RHAMM), and growth factors (transforming growth factor\u2010\u03b23 [TGF\u2010\u03b23] and fibroblast growth factor 14 [FGF14]). A second group of genes were suggestive of active axonal myelination. These genes mediate survival of immature cells after contact with newly produced axonal matrix (laminin B1, collagens, integrin alpha 6) and stabilization of myelinating glia\u2010axon contacts (RAB13, contactins 3 and 4). A third group indicated the appearance and\/or upregulation of mature processes. The latter included genes for: K+ channels (TASK\u20101, TASK\u20105), intercellular junctions (connexin30), neurotransmitter receptors (adrenergic alpha 1B, kainate 2, serotonin 7, GABA\u2010A), as well as major proteins responsible for their transport and\/or anchoring (Homer 1, MAGUK MPP3, Shank2). All these genes were possibly involved in synaptic plasticity, namely the formation, maturation, and stabilization of new neural connections within the striatum. MPH treatment seems to potentiate synaptic plasticity, which is an age\u2010dependent developmental phenomenon that adolescent rats are very likely to show, compared to adults. Our observations suggest that adolescent MPH exposure causes only transient changes in reproductive and hormonal parameters, and a more enduring enhancement of neurobehavioral plasticity.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1369.005","type":"journal-article","created":{"date-parts":[[2006,11,15]],"date-time":"2006-11-15T21:45:57Z","timestamp":1163627157000},"page":"52-73","source":"Crossref","is-referenced-by-count":65,"title":["Short\u2010Term Effects of Adolescent Methylphenidate Exposure on Brain Striatal Gene Expression and Sexual\/Endocrine Parameters in Male Rats"],"prefix":"10.1111","volume":"1074","author":[{"given":"WALTER","family":"ADRIANI","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DAMIANA","family":"LEO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MARIA","family":"GUARINO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ALESSIA","family":"NATOLI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EMMA","family":"DI CONSIGLIO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GIOVANNA","family":"DE ANGELIS","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ELSA","family":"TRAINA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EMANUELA","family":"TESTAI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CARLA","family":"PERRONE\u2010CAPANO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GIOVANNI","family":"LAVIOLA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,9,6]]},"reference":[{"key":"e_1_2_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(97)00170-8"},{"key":"e_1_2_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2003.08.005"},{"key":"e_1_2_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(01)00433-8"},{"key":"e_1_2_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2004.06.021"},{"key":"e_1_2_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(01)00281-0"},{"key":"e_1_2_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn777"},{"key":"e_1_2_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2003.08.020"},{"key":"e_1_2_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(03)00570-5"},{"key":"e_1_2_4_10_2","article-title":"Methylphenidate administration to adolescent rats determines short\u2010 and long\u2010term changes on reward\u2010related behavior and striatal gene expression","author":"Adriani W.","year":"2005","journal-title":"Neuropsychopharmacology"},{"key":"e_1_2_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2004.06.031"},{"key":"e_1_2_4_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02892.x"},{"key":"e_1_2_4_13_2","first-page":"1","article-title":"Topography of methylphenidate (Ritalin)\u2010induced gene regulation in the striatum: differential effects on c\u2010Fos, substance P and opioid peptides","volume":"22","author":"Yano M.","year":"2004","journal-title":"Neuropsychopharmacology"},{"key":"e_1_2_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0892-0362(87)90086-9"},{"key":"e_1_2_4_15_2","first-page":"545","article-title":"The effects of chronic methylphenidate treatment on the groth and endocrine function in the developing rat","volume":"215","author":"Greelcy G.H.","year":"1980","journal-title":"J. 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