TY - JOUR
T1 - Neurobehavioral and neurodevelopmental profiles of a heuristic genetic model of differential schizophrenia- and addiction-relevant features
T2 - The RHA vs. RLA rats
AU - Fernández-Teruel, Alberto
AU - Oliveras, Ignasi
AU - Cañete, Toni
AU - Rio-Álamos, Cristóbal
AU - Tapias-Espinosa, Carles
AU - Sampedro-Viana, Daniel
AU - Sánchez-González, Ana
AU - Sanna, Francesco
AU - Torrubia, Rafael
AU - González-Maeso, Javier
AU - Driscoll, Peter
AU - Morón, Ignacio
AU - Torres, Carmen
AU - Aznar, Susana
AU - Tobeña, Adolf
AU - Corda, Maria G
AU - Giorgi, Osvaldo
N1 - Copyright © 2021 Elsevier Ltd. All rights reserved.
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85116455132&partnerID=8YFLogxK
U2 - 10.1016/j.neubiorev.2021.09.042
DO - 10.1016/j.neubiorev.2021.09.042
M3 - Review
C2 - 34571119
SN - 0149-7634
VL - 131
SP - 597
EP - 617
JO - Neuroscience and Biobehavioral Reviews
JF - Neuroscience and Biobehavioral Reviews
ER -