{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:35:43Z","timestamp":1791027343951,"version":"4.1.0"},"reference-count":73,"publisher":"National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,9,25]]},"abstract":"<jats:p>\n                    In the brain, dopamine exerts an important modulatory influence\n over behaviors such as emotion, cognition, and affect as well as\n mechanisms of reward and the control of locomotion. The dopamine\n transporter (DAT), which reuptakes the released neurotransmitter into\n presynaptic terminals, is a major determinant of the intensity and\n duration of the dopaminergic signal. Knockout mice lacking the dopamine\n transporter (DAT-KO mice) display marked changes in dopamine\n homeostasis that result in elevated dopaminergic tone and pronounced\n locomotor hyperactivity. A feature of DAT-KO mice is that their\n hyperactivity can be inhibited by psychostimulants and serotonergic\n drugs. The pharmacological effect of these drugs occurs without any\n observable changes in dopaminergic parameters, suggesting that other\n neurotransmitter systems in addition to dopamine might contribute to\n the control of locomotion in these mice. We report here that the\n hyperactivity of DAT-KO mice can be markedly further enhanced when\n                    <jats:italic>N-<\/jats:italic>\n                    methyl-\n                    <jats:sc>d<\/jats:sc>\n                    -aspartate receptor-mediated\n glutamatergic transmission is blocked. Conversely, drugs that enhance\n glutamatergic transmission, such as positive modulators of\n                    <jats:sc>l<\/jats:sc>\n                    -\u03b1-amino-3-hydroxy-5-methylisoxazole-4-propionate\n glutamate receptors, suppress the hyperactivity of DAT-KO mice.\n Interestingly, blockade of\n                    <jats:italic>N-<\/jats:italic>\n                    methyl-\n                    <jats:sc>d<\/jats:sc>\n                    -aspartate receptors prevented\n the inhibitory effects of both psychostimulant and serotonergic drugs\n on hyperactivity. These findings support the concept of a reciprocal\n functional interaction between dopamine and glutamate in the basal\n ganglia and suggest that agents modulating glutamatergic transmission\n may represent an approach to manage conditions associated with\n dopaminergic dysfunction.\n                  <\/jats:p>","DOI":"10.1073\/pnas.191353298","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:10Z","timestamp":1027679650000},"page":"11047-11054","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":150,"title":["Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter"],"prefix":"10.1073","volume":"98","author":[{"given":"Raul R.","family":"Gainetdinov","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute Laboratories, Departments of Cell\r Biology and Medicine, Duke University Medical Center, Durham, NC 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