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Science 325 (5943): 1017-1020

Copyright © 2009 by the American Association for the Advancement of Science

Dopamine Controls Persistence of Long-Term Memory Storage

Janine I. Rossato,1,2 Lia R. M. Bevilaqua,1,2 Iván Izquierdo,1,2 Jorge H. Medina,1,3,4 Martín Cammarota1,2,3,*

Abstract: The paradigmatic feature of long-term memory (LTM) is its persistence. However, little is known about the mechanisms that make some LTMs last longer than others. In rats, a long-lasting fear LTM vanished rapidly when the D1 dopamine receptor antagonist SCH23390 was injected into the dorsal hippocampus 12 hours, but not immediately or 9 hours, after the fearful experience. Conversely, intrahippocampal application of the D1 agonist SK38393 at the same critical post-training time converted a rapidly decaying fear LTM into a persistent one. This effect was mediated by brain-derived neurotrophic factor and regulated by the ventral tegmental area (VTA). Thus, the persistence of LTM depends on activation of VTA/hippocampus dopaminergic connections and can be specifically modulated by manipulating this system at definite post-learning time points.

1 Centro de Memória, Instituto do Cérebro, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
2 Instituto Nacional de Neurociência Translacional, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil.
3 Instituto de Biología Celular y Neurociencias "Prof. Dr. Eduardo de Robertis," Universidad de Buenos Aires, Buenos Aires, Argentina.
4 Departamento de Fisiologia, Universidad de Buenos Aires, Buenos Aires, Argentina.

* To whom correspondence should be addressed. E-mail: mcammaro{at} or martin.cammarota{at}

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