What is it about?
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) dendritic 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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Why is it important?
The Roman High-Avoidance (RHA) rat line is important because it serves as a model for studying neurodevelopmental aspects of schizophrenia and drug addiction vulnerability. Key features include increased impulsivity, cognitive deficits, and specific neurobiological alterations such as changes in dopamine and serotonin systems. This model helps researchers understand the genetic and neurochemical underpinnings of these disorders, potentially leading to new therapeutic approaches.
Perspectives
The Roman High-Avoidance (RHA) and Low-Avoidance (RLA) rat lines offer valuable perspectives for research in psychiatric disorders, particularly schizophrenia and addiction. They provide insights into the genetic basis of behavior, neurobiological mechanisms of cognitive and emotional processing, and potential therapeutic approaches. These well-characterized models bridge preclinical and clinical research, promising to advance our understanding of complex neuropsychiatric conditions and their underlying mechanisms.
Carles Tapias Espinosa
Read the Original
This page is a summary of: Neurobehavioral and neurodevelopmental profiles of a heuristic genetic model of differential schizophrenia- and addiction-relevant features: The RHA vs. RLA rats, Neuroscience & Biobehavioral Reviews, December 2021, Elsevier,
DOI: 10.1016/j.neubiorev.2021.09.042.
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