Genetic Disruption of Arc/Arg3.1 in Mice Causes Alterations in Dopamine and Neurobehavioral Phenotypes Related to Schizophrenia.
Cell Rep
; 16(8): 2116-2128, 2016 08 23.
Article
en En
| MEDLINE
| ID: mdl-27524619
ABSTRACT
Human genetic studies have recently suggested that the postsynaptic activity-regulated cytoskeleton-associated protein (Arc) complex is a convergence signal for several genes implicated in schizophrenia. However, the functional significance of Arc in schizophrenia-related neurobehavioral phenotypes and brain circuits is unclear. Here, we find that, consistent with schizophrenia-related phenotypes, disruption of Arc in mice produces deficits in sensorimotor gating, cognitive functions, social behaviors, and amphetamine-induced psychomotor responses. Furthermore, genetic disruption of Arc leads to concomitant hypoactive mesocortical and hyperactive mesostriatal dopamine pathways. Application of a D1 agonist to the prefrontal cortex or a D2 antagonist in the ventral striatum rescues Arc-dependent cognitive or psychomotor abnormalities, respectively. Our findings demonstrate a role for Arc in the regulation of dopaminergic neurotransmission and related behaviors. The results also provide initial biological support implicating Arc in dopaminergic and behavioral abnormalities related to schizophrenia.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Trastornos Psicomotores
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Esquizofrenia
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Dopamina
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Proteínas del Citoesqueleto
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Disfunción Cognitiva
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Proteínas del Tejido Nervioso
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
Cell Rep
Año:
2016
Tipo del documento:
Article
País de afiliación:
Italia