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We utilized mice that exhibit elevated synaptic noradrenaline (NA) by genetically deleting the noradrenaline transporter (NET), a key regulator of the noradrenergic system (NET KO mice). NET KO and wild\u2010type littermates were administered MPTP and striatal dopamine terminal integrity was assessed by HPLC of monoamines, immmunoblotting for dopaminergic markers and tyrosine hydroxylase (TH) immunohistochemistry. MPTP significantly reduced striatal dopamine in wild\u2010type mice, but not in the NET KO mice. To confirm that the protection observed in the NET KO mice was due to the lack of NET, we treated wild\u2010type mice with the specific NET inhibitor, nisoxetine, and then challenged them with MPTP. Nisoxetine conferred protection to the dopaminergic system. These data indicate that NA can modulate MPTP toxicity and suggest that manipulation of the noradrenergic system may have therapeutic value in PD.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2004.02785.x","type":"journal-article","created":{"date-parts":[[2004,11,18]],"date-time":"2004-11-18T17:56:31Z","timestamp":1100800591000},"page":"1116-1124","source":"Crossref","is-referenced-by-count":67,"title":["Reduced MPTP toxicity in noradrenaline transporter knockout mice"],"prefix":"10.1111","volume":"91","author":[{"given":"Karen S.","family":"Rommelfanger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Weinshenker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary W.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,11,18]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1101\/lm.6.3.216","article-title":"Activity\u2010dependent activation of TrkB neurotrophin receptors in the adult CNS","volume":"6","author":"Aloyz R.","year":"1999","journal-title":"Learn. 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