Neurobehavioral and neurodevelopmental profiles of a heuristic genetic model of differential schizophrenia- and addiction-relevant features: The RHA vs. RLA rats. (December 2021)

• Record Type: Journal Article
• Authors: Fernández-Teruel, Alberto; Oliveras, Ignasi; Cañete, Toni; Rio-Álamos, Cristóbal; Tapias-Espinosa, Carles; Sampedro-Viana, Daniel; Sánchez-González, Ana; Sanna, Francesco; Torrubia, Rafael; González-Maeso, Javier; Driscoll, Peter; Morón, Ignacio; Torres, Carmen; Aznar, Susana; Tobeña, Adolf; Corda, Maria G.; Giorgi, Osvaldo
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 131(2021)
• Page Start: 597
• Page End: 617
• Publication Date: 2021-12
• Subjects: Roman high- and low-avoidance rats -- Neurodevelopmental genetic model -- Schizophrenia-relevant features -- Glutamate -- GABA -- Mesocorticolimbic dopaminergic pathways -- Nucleus accumbens -- Medial prefrontal cortex -- Hippocampus; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2021.09.042
• Languages: English
• ISSNs: 0149-7634

Abstract

Highlights: RHA vs. RLA rats are a model of neurodevelopmental schizophrenia-relevant features. RHA vs. RLA rats are a model of differential drug addiction-related features. RHA rats present hypofunction of the prefrontal cortex and hippocampus. A developmental glutamatergic deficit can underlie the phenotypic profile of RHA rats. 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.