{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:20:47Z","timestamp":1791051647118,"version":"4.1.0"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,10,15]]},"abstract":"<jats:p>\n                    Acute pharmacological blockade of \u03b11 adrenoreceptors (ARs) attenuates the locomotor response to amphetamine (LRA). We took a genetic approach to study how norepinephrine (NE) signaling modulates psychostimulant responses by testing LRA in dopamine \u03b2-hydroxylase knockout (\n                    <jats:italic>Dbh<\/jats:italic>\n                    \u2212\/\u2212) mice that lack NE. Surprisingly,\n                    <jats:italic>Dbh<\/jats:italic>\n                    \u2212\/\u2212 animals were hypersensitive to the behavioral effects of amphetamine. Amphetamine (2 mg\/kg) elicited greater locomotor activity in\n                    <jats:italic>Dbh<\/jats:italic>\n                    \u2212\/\u2212 mice compared to controls, whereas 5 mg\/kg caused stereotypy in\n                    <jats:italic>Dbh<\/jats:italic>\n                    \u2212\/\u2212 mice, which is only observed in control mice at higher doses. Prazosin, an \u03b11AR antagonist, attenuated LRA in\n                    <jats:italic>Dbh<\/jats:italic>\n                    +\/\u2212 mice but had no effect in\n                    <jats:italic>Dbh<\/jats:italic>\n                    \u2212\/\u2212 mice. Changes in the sensitivity of dopamine (DA)-signaling pathways may contribute to the altered amphetamine responses of\n                    <jats:italic>Dbh<\/jats:italic>\n                    \u2212\/\u2212 mice because they were relatively insensitive to a D1 agonist and hypersensitive to a D2 agonist. Daily amphetamine administration resulted in behavioral sensitization in both\n                    <jats:italic>Dbh<\/jats:italic>\n                    +\/\u2212 and\n                    <jats:italic>Dbh<\/jats:italic>\n                    \u2212\/\u2212 mice, demonstrating that NE is not required for the development or expression of behavioral sensitization. Daily prazosin administration blunted but did not completely block locomotor sensitization in\n                    <jats:italic>Dbh<\/jats:italic>\n                    +\/\u2212 mice, suggesting that \u03b11AR signaling contributes to, but is not required for sensitization in\n                    <jats:italic>Dbh<\/jats:italic>\n                    +\/\u2212 control animals. We conclude that in contrast to acute \u03b11AR blockade, chronic NE deficiency induces changes similar to sensitization, perhaps by altering DA-signaling pathways.\n                  <\/jats:p>","DOI":"10.1073\/pnas.212519999","type":"journal-article","created":{"date-parts":[[2002,10,15]],"date-time":"2002-10-15T12:43:03Z","timestamp":1034685783000},"page":"13873-13877","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":97,"title":["Mice with chronic norepinephrine deficiency resemble amphetamine-sensitized animals"],"prefix":"10.1073","volume":"99","author":[{"given":"David","family":"Weinshenker","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole S.","family":"Miller","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Department 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