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It is believed that the locomotor\u2010stimulating action of \u03b2\u2010PEA, much like amphetamine, depends on its ability to increase extracellular dopamine (DA) concentrations owing to reversal of the direction of dopamine transporter (DAT)\u2010mediated DA transport. \u03b2\u2010PEA can also bind directly to the recently identified G protein\u2010coupled receptors, but the physiological significance of this interaction is unclear. To assess the mechanism by which \u03b2\u2010PEA mediates its effects, we compared the neurochemical and behavioral effects of this amine in wild type (WT), heterozygous and \u2018null\u2019 DAT mutant mice. In microdialysis studies, \u03b2\u2010PEA, administered either systemically or locally via intrastriatal infusion, produced a pronounced outflow of striatal DA in WT mice whereas no increase was detected in mice lacking the DAT (DAT\u2010KO mice). Similarly, in fast\u2010scan voltammetry studies \u03b2\u2010PEA did not alter DA release and clearance rate in striatal slices from DAT\u2010KO mice. In behavioral studies \u03b2\u2010PEA produced a robust but transient increase in locomotor activity in WT and heterozygous mice. In DAT\u2010KO mice, whose locomotor activity and stereotypy are increased in a novel environment, \u03b2\u2010PEA (10\u2013100\u2003mg\/kg) exerted a potent inhibitory action. At high doses, \u03b2\u2010PEA induced stereotypies in WT and heterozygous mice; some manifestations of stereotypy were also observed in the DAT\u2010KO mice. These data demonstrate that the DAT is required for the striatal DA\u2010releasing and hyperlocomotor actions of \u03b2\u2010PEA. The inhibitory action on hyperactivity and certain stereotypies induced by \u03b2\u2010PEA in DAT\u2010KO mice indicate that targets other than the DAT are responsible for these effects.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2004.02721.x","type":"journal-article","created":{"date-parts":[[2004,9,24]],"date-time":"2004-09-24T12:55:31Z","timestamp":1096030531000},"page":"362-373","source":"Crossref","is-referenced-by-count":68,"title":["Dopamine transporter\u2010dependent and \u2010independent actions of trace amine \u03b2\u2010phenylethylamine"],"prefix":"10.1111","volume":"91","author":[{"given":"Tatyana D.","family":"Sotnikova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgeny A.","family":"Budygin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara R.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda A.","family":"Dykstra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc G.","family":"Caron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raul R.","family":"Gainetdinov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,9,10]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0376-8716(98)00068-4"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00979534"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(91)90207-3"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00966752"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300343"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00757-1"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130100890"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.151105198"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80353-0"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5846(82)80150-4"},{"key":"e_1_2_16_12_1","first-page":"13","volume-title":"Neurobiology of the Trace Amines","author":"Boulton A. 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