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

Alberto Fernández-Teruel, Ignasi Oliveras, Toni Cañete, Cristóbal Rio-Álamos, Carles Tapias-Espinosa, Daniel Sampedro-Viana, Ana Sánchez-González, Francesco Sanna, Rafael Torrubia, Javier González-Maeso, Peter Driscoll, Ignacio Morón, Carmen Torres, Susana Aznar, Adolf Tobeña, Maria G Corda, Osvaldo Giorgi

Abstract

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.

OriginalsprogEngelsk
TidsskriftNeuroscience and Biobehavioral Reviews
Vol/bind131
Sider (fra-til)597-617
Antal sider21
ISSN0149-7634
DOI
StatusUdgivet - dec. 2021

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