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It has been proposed that AMA can indirectly modulate dopaminergic transmission. In high doses, the central nervous system is its primary site of toxicity. To examine deleterious effects on CNS induced by AMA, this study evaluated possible neurobehavioral alterations induced by AMA such as stereotyped behavior, the effects on locomotion and memory and its possible genotoxic\/mutagenic activities. Adult male CF\u20101 mice were treated with a systemic injection of AMA (15, 30 or 60\u2009mg kg<jats:sup>\u22121<\/jats:sup>) 20\u2009min before behavioral tasks on open field and inhibitory avoidance. Higher AMA doses increased the latency to step\u2010down inhibitory avoidance test in the training session in the inhibitory avoidance task. At 60\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup> AMA induced impairing effects on locomotion and exploration and hence impaired habituation to a novel environment. Stereotyped behavior after each administration in a 3\u2010day trial was observed, suggesting effects on dopaminergic system. Amantadine was not able to induce chromosomal mutagenesis or toxicity on bone marrow, as evaluated by the micronucleus assay. At the lowest dose tested, AMA did not induce DNA damage and it was unable to impair memory, locomotion, exploration or motivation in mice. However, higher AMA doses increased DNA damage in brain tissue, produced locomotor disturbances severe enough to preclude testing for learning and memory effects, and induced stereotypy, suggesting neurotoxicity.<\/jats:p>","DOI":"10.1002\/jat.1550","type":"journal-article","created":{"date-parts":[[2010,6,23]],"date-time":"2010-06-23T08:43:24Z","timestamp":1277282604000},"page":"745-753","source":"Crossref","is-referenced-by-count":22,"title":["DNA damage in brain cells and behavioral deficits in mice after treatment with high doses of amantadine"],"prefix":"10.1002","volume":"30","author":[{"given":"Vanessa","family":"Kaefer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliane Garcia","family":"Semedo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivian Franc\u00edlia","family":"Silva Kahl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael Gomes","family":"Von Borowsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana\u00edna","family":"Gianesini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tarso Benigno","family":"Ledur Kist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patr\u00edcia","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaqueline Nascimento","family":"Picada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,11,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(92)90182-G"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.05.014"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2008.10.011"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4883-05.2006"},{"key":"e_1_2_6_6_1","first-page":"467","article-title":"Glucocorticoids modulate behavioral effects induced by dopaminergic agonists in rats","volume":"53","author":"Danilczuk Z","year":"2001","journal-title":"Pol. 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