Neurobehavioral and neurodevelopmental profiles of a heuristic genetic model of differential schizophrenia- and addiction-relevant features: The RHA vs. RLA rats

The Roman High- (RHA) and Low-(RLA) avoidance rat lines/strains were generated through bidirectional selective breeding for rapid (RHA) vs. extremely poor (RLA) two-way active avoidance acquisition. Compared with RLAs and other rat strains/stocks, RHAs are characterized by increased impulsivity, def...

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Detalles Bibliográficos
Autores: Fernández-Teruel, Alberto|||0000-0001-5993-7058, Oliveras, Ignasi|||0000-0002-3082-0355, Cañete, Toni|||0000-0002-8950-8120, Río-Álamos, Cristóbal|||0000-0002-5676-4494, Tapias-Espinosa, Carles|||0000-0003-3110-0138, Sampedro-Viana, Daniel|||0000-0003-3922-4039, Sánchez González, Ana, Sanna, Francesco|||0000-0002-3382-2508, Torrúbia, Rafael|||0000-0002-6826-6572, Gonzalez-Maeso, Javier|||0000-0003-3105-3204, Driscoll, Peter, Morón, Ignacio, Torres, Carmen, Aznar, Susana|||0000-0001-7940-6246, Tobeña, Adolf|||0000-0001-6137-0660, Corda, Maria G., Giorgi, Osvaldo|||0000-0003-4610-8183
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:285963
Acceso en línea:https://ddd.uab.cat/record/285963
https://dx.doi.org/urn:doi:10.1016/j.neubiorev.2021.09.042
Access Level:acceso abierto
Palabra clave:GABA
Glutamate
Hippocampus
Medial prefrontal cortex
Mesocorticolimbic dopaminergic pathways
Neurodevelopmental genetic model
Nucleus accumbens
Roman high- and low-avoidance rats
Schizophrenia-relevant features
Descripción
Sumario:The Roman High- (RHA) and Low-(RLA) avoidance rat lines/strains were generated through bidirectional selective breeding for rapid (RHA) vs. extremely poor (RLA) two-way active avoidance acquisition. Compared with RLAs and other rat strains/stocks, RHAs are characterized by increased impulsivity, deficits in social behavior, novelty-induced hyper-locomotion, impaired attentional/cognitive abilities, vulnerability to psychostimulant sensitization and drug addiction. RHA rats also exhibit decreased function of the prefrontal cortex (PFC) and hippocampus, increased functional activity of the mesolimbic dopamine system and a dramatic deficit of central metabotropic glutamate-2 (mGlu2) receptors (due to a stop codon mutation at cysteine 407 in Grm2 -cys407*-), along with increased density of 5-HT2A receptors in the PFC, alterations of several synaptic markers and increased density of pyramidal "thin" (immature) dendrític spines in the PFC. These characteristics suggest an immature brain of RHA rats, and are reminiscent of schizophrenia features like hypofrontality and disruption of the excitation/inhibition cortical balance. RHA rats represent a promising heuristic model of neurodevelopmental schizophrenia-relevant features and comorbidity with drug addiction vulnerability.

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