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| Home > Articles > Published articles > Neurobehavioral and neurodevelopmental profiles of a heuristic genetic model of differential schizophrenia- and addiction-relevant features: The RHA vs. RLA rats |
(Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal) (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal) (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal) (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal) (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal) (Universitá di Cagliari. Dipartimento di Scienze della vita e dell'ambiente) (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal) (Bispebjerg and Frederiksberg Hospitals (Copenhagen, Dinamarca)) (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal) (Universitá di Cagliari. Dipartimento di Scienze della vita e dell'ambiente)| Date: | 2021 |
| 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. |
| Grants: | Agencia Estatal de Investigación PID2020-114697GB-I00 Agencia Estatal de Investigación PSI2017-82257-P Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR-1586 Agencia Estatal de Investigación PSI2017-87340-P Agencia Estatal de Investigación FJC2018-038808-I Ministerio de Educación, Ciencia y Deporte FPU15/06307 |
| Note: | Altres ajuts: ICREA-Academia 2013; ARS, L.R. 7/2007, Ref. CRP-59842; NIH R01 MH084894, NIH R01 MH111940 and NIH-P30DA033934; the Bispebjerg Hospital Research Council;FONDECYT INICIACION 11190240 (Chile). |
| Rights: | Tots els drets reservats.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió acceptada per publicar |
| Subject: | GABA ; Glutamate ; Hippocampus ; Medial prefrontal cortex ; Mesocorticolimbic dopaminergic pathways ; Neurodevelopmental genetic model ; Nucleus accumbens ; Roman high- and low-avoidance rats ; Schizophrenia-relevant features |
| Published in: | Neuroscience and Biobehavioral Reviews, Vol. 131 (2021) , p. 597-617, ISSN 1873-7528 |
