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We studied whether a persistent cognitive\/emotional dysregulation in mice withdrawn from cocaine holds a neurobiological correlate within the hippocampus, a limbic region with a key role in anxiety and memory but that has been scarcely investigated in cocaine addiction research. Mice were submitted to a chronic cocaine (20 mg\/kg\/day for 12 days) or vehicle treatment followed by 44 drug-free days. Some mice were then assessed on a battery of emotional (elevated plus-maze, light\/dark box, open field, forced swimming) and cognitive (object and place recognition memory, cocaine-induced conditioned place preference, continuous spontaneous alternation) behavioral tests, while other mice remained in their home-cage. Relevant hippocampal features [basal c-Fos activity, GABA+, parvalbumin (PV)+ and neuropeptide Y (NPY)+ interneurons, and adult neurogenesis (cell proliferation and immature neurons)] were immunohistochemically assessed 73 days after the chronic cocaine or vehicle protocol. The cocaine-withdrawn mice showed no remarkable exploratory or emotional alterations but were consistently impaired in all the cognitive tasks. All the cocaine-withdrawn groups, independently of whether they were submitted to behavioral assessment or not, showed enhanced basal c-Fos expression and increased number of GABA+ cells in the dentate gyrus. Moreover, the cocaine-withdrawn mice previously submitted to behavioral training displayed a blunted experience-dependent regulation of the dentate gyrus' PV+ and NPY+ neurons, and adult hippocampal neurogenesis. Results highlight the importance of hippocampal neuroplasticity for the ingrained cognitive deficits present during chronic cocaine withdrawal.<\/jats:p>","DOI":"10.1242\/dmm.026682","type":"journal-article","created":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T01:25:25Z","timestamp":1485825925000},"source":"Crossref","is-referenced-by-count":28,"title":["Long-lasting memory deficits in mice withdrawn from cocaine are concomitant to neuroadaptations in hippocampal basal activity, GABAergic interneurons and adult neurogenesis"],"prefix":"10.1242","author":[{"given":"David Ladr\u00f3n","family":"de Guevara-Miranda","sequence":"first","affiliation":[{"name":"Departamento de Psicobiolog\u00eda y Metodolog\u00eda de las Ciencias del Comportamiento, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), Facultad de Psicolog\u00eda, Universidad de M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmelo","family":"Mill\u00f3n","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), Facultad de Medicina, Universidad de M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Rosell-Valle","sequence":"additional","affiliation":[{"name":"Departamento de Psicobiolog\u00eda y Metodolog\u00eda de las Ciencias del Comportamiento, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), Facultad de Psicolog\u00eda, Universidad de M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"P\u00e9rez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa (CABIMER), Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Missiroli","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa (CABIMER), Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Serrano","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Salud Mental, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), Hospital Regional Universitario de M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco J.","family":"Pav\u00f3n","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Salud Mental, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), Hospital Regional Universitario de M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando Rodr\u00edguez","family":"de Fonseca","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Salud Mental, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), Hospital Regional Universitario de M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Mart\u00ednez-Losa","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa (CABIMER), Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"\u00c1lvarez-Dolado","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda Molecular y Medicina Regenerativa (CABIMER), Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis J.","family":"Sant\u00edn","sequence":"additional","affiliation":[{"name":"Departamento de Psicobiolog\u00eda y Metodolog\u00eda de las Ciencias del Comportamiento, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), Facultad de Psicolog\u00eda, Universidad de M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4496-1167","authenticated-orcid":false,"given":"Estela","family":"Castilla-Ortega","sequence":"additional","affiliation":[{"name":"Departamento de Psicobiolog\u00eda y Metodolog\u00eda de las Ciencias del Comportamiento, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), Facultad de Psicolog\u00eda, Universidad de M\u00e1laga, Spain"},{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Salud Mental, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), Hospital Regional Universitario de M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2017,1,1]]},"reference":[{"key":"2021042500052191200_DMM026682C1","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.biopsych.2014.12.027","article-title":"Basal hippocampal activity and its functional connectivity predicts cocaine relapse","volume":"78","author":"Adinoff","year":"2015","journal-title":"Biol. 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