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.
Genetic Disruption of Arc/Arg3.1 in Mice Causes Alterations in Dopamine and Neurobehavioral Phenotypes Related to Schizophrenia / F. Manago, M. Mereu, S. Mastwal, R. Mastrogiacomo, D. Scheggia, M. Emanuele, M.A. De Luca, D.R. Weinberger, K.H. Wang, F. Papaleo. - In: CELL REPORTS. - ISSN 2211-1247. - 16:8(2016), pp. 2116-2128.
|Titolo:||Genetic Disruption of Arc/Arg3.1 in Mice Causes Alterations in Dopamine and Neurobehavioral Phenotypes Related to Schizophrenia|
|Parole Chiave:||ventral tegmental area; amphetamine-induced activity; medial prefrontal cortex; immediate-early gene; temporal-order; prepulse inhibition; synaptic plasticity; recognition memory; nucleus-accumbens; pyramidal neurons|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.celrep.2016.07.044|
|Appare nelle tipologie:||01 - Articolo su periodico|