1. Neurobehavioral and neurodevelopmental profiles of a heuristic genetic model of differential schizophrenia- and addiction-relevant features: The RHA vs. RLA rats
- Author
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Carmen Torres, Francesco Sanna, Rafael Torrubia, Daniel Sampedro-Viana, Ignasi Oliveras, Toni Cañete, Javier González-Maeso, Cristóbal Río-Álamos, Ignacio Morón, Alberto Fernández-Teruel, Ana Sánchez-González, Carles Tapias-Espinosa, Peter Driscoll, Osvaldo Giorgi, Maria Giuseppa Corda, Susana Aznar, and Adolf Tobeña
- Subjects
Dendritic spine ,Models, Genetic ,Cognitive Neuroscience ,Prefrontal Cortex ,Hippocampus ,Hypofrontality ,Biology ,Nucleus accumbens ,Rats ,Behavior, Addictive ,Behavioral Neuroscience ,Neuropsychology and Physiological Psychology ,Metabotropic receptor ,Genetic model ,Avoidance Learning ,Schizophrenia ,Animals ,Heuristics ,Prefrontal cortex ,Neuroscience ,Addiction vulnerability - 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.
- Published
- 2021