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

Fernández-Teruel, Alberto; Oliveras, Ignasi; Cañete, Toni; Río-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 Giuseppa; Giorgi, Osvaldo

doi:10.1016/j.neubiorev.2021.09.042

Cited by 20 publications

(30 citation statements)

References 375 publications

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“…Selection for poor two-way active avoidance task acquisition led to behaviorally inhibited, high "neuroticism" and "internalizing" Roman low-avoidance rats Thus, when facing different types of threatening situations, RLA rats are predominantly high freezers, displaying behavioral inhibition and a passive coping style (opposite to the trait profiles of RHA rats, as we will see below; see also reviews by Driscoll et al, 1998;Fernández-Teruel et al, 2021;Steimer & Driscoll, 2003;Giorgi et al, 2019). These trait differences generalize to many between-strain phenotype differences in conditioned and unconditioned tests/tasks reflecting coping style of fear-, anxiety-and depression-related responses.…”

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confidence: 96%

“…Over 270 international articles have been published on the Roman rats (or using them as part of broader studies) during the past fifty-five years. They have been used for psychological, neurobiological and genetic research purposes in over 20 different laboratories around the world (see Supplementary Table S1, in Fernández-Teruel et al, 2021), and continue to be very productive, as shown by the over 35 papers published in the past five years.…”

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confidence: 99%

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Contribution of the Roman rat lines/strains to personality neuroscience: neurobehavioral modeling of internalizing/externalizing psychopathologies

Fernández-Teruel,

Cañete,

Sampedro-Viana

et al. 2023

Personality Neuroscience

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The Roman high-avoidance (RHA) and low-avoidance (RLA) rat lines/strains were established in Rome through bidirectional selection of Wistar rats for rapid (RHA) or extremely poor (RLA) acquisition of a two-way active avoidance task. Relative to RHAs, RLA rats exhibit enhanced threat sensitivity, anxiety, fear and vulnerability to stress, a passive coping style and increased sensitivity to frustration. Thus, RLA rats’ phenotypic profile falls well within the “internalizing” behavior spectrum. Compared with RLAs and other rat strains/stocks, RHAs present increased impulsivity and reward sensitivity, deficits in social behavior and attentional/cognitive processes, novelty-induced hyper-locomotion and vulnerability to psychostimulant sensitization and drug addiction. Thus, RHA rats’ phenotypes are consistent with a “disinhibiting externalizing” profile. Many neurobiological/molecular traits differentiate both rat lines/strains. For example, relative to RLA rats, RHAs exhibit decreased function of the prefrontal cortex (PFC), hippocampus and amygdala, increased functional tone of the mesolimbic dopamine system, a deficit of central metabotropic glutamate-2 (mGlu2) receptors, increased density of serotonin 5-HT2A receptors in the PFC, impairment of GABAergic transmission in the PFC, alterations of several synaptic markers and increased density of pyramidal 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. We review evidence supporting RLA rats as a valid model of anxiety/fear, stress and frustration vulnerability, whereas RHA rats represent a promising translational model of neurodevelopmental alterations related to impulsivity, schizophrenia-relevant features and comorbidity with drug addiction vulnerability.

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confidence: 96%

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confidence: 99%

Contribution of the Roman rat lines/strains to personality neuroscience: neurobehavioral modeling of internalizing/externalizing psychopathologies

Fernández-Teruel,

Cañete,

Sampedro-Viana

et al. 2023

Personality Neuroscience

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“…In parental opioid exposure, it is clear that opioids induce plastic dopaminergic alterations in the mesocorticolimbic system (Vousooghi et al., 2018). There is a relationship between the glutamatergic and dopaminergic systems (Fernandez‐Teruel et al., 2021). Therefore, the behavioral outcome is a result of dopaminergic and glutamatergic plastic modifications in the brain.…”

Section: Discussionmentioning

confidence: 99%

Neonatal olfactory bulbectomy induces anxiety‐related behavior and modifies dopaminergic receptor expression in post‐pubertal rats

Flores

Gómez-Villalobos

Iannitti

et al. 2023

Synapse

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Olfaction is a complex physiological process producing effects in the central nervous system (CNS) and implicated in emotional processes. Indeed, the olfactory bulbs (OB) send projections to various CNS regions including the nucleus accumbens (NAcc) and caudate-putamen (CPu). Both the NAcc and CPu receive important dopaminergic input. Emerging evidence suggests that dopamine (DA) is related to anxiety-related behaviors. Therefore, we aimed to investigate the consequences of neonatal olfactory bulbectomy (nOBX) to anxiety-related behavior as assayed in the elevated plus maze (EPM) as well as the expression of dopaminergic receptors (D1-like, D2-like, and D3) in the NAcc and CPu at pre-and post-pubertal ages in the rat. The results show that nOBX increased the number of entries in the open arm of the EPM post-pubertally, suggesting an anxiolytic-related effect. nOBX increased the D2-like binding in the NAcc shell and D3 binding in the NAcc core pre-pubertally. At post-pubertal ages, the D3 binding was reduced at the olfactory tubercle and islands of Calleja in nOBX rats. Alterations in the DA receptor expression may be one mechanism responsible for the observed behavioral modifications in nOBX rats.

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“…Further studies are required to verify whether the sexual activityinduced differential changes in BDNF, trkB, and Arc levels in the dHC and vHC are causal and/or consequent to the higher sexual motivation and performance of RHA versus RLA rats. Moreover, it is likely that the changes in the expression of BDNF, trkB, c-Fos, ΔFosB, and Arc between the sexually naïve and the experienced Roman rats that occur in the hippocampus, and in the limbic system in general, may all play a role in the characteristic Roman line differences not only in sexual behavior but also in other motivated behaviors, and their alterations (Fernández-Teruel et al, 2021;Giorgi et al, 2007Giorgi et al, , 2019Melis et al, 2019;Serra et al, 2018).…”

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Neuroplastic changes inc‐Fos,ΔFosB,BDNF,trkB, and Arc expression in the hippocampus of male Roman rats: differential effects of sexual activity

et al. 2022

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Sexual activity causes differential changes in the expression of markers of neural activation (c-Fos and ΔFosB) and neural plasticity (Arc and BDNF/trkB), as determined either by Western Blot (BDNF, trkB, Arc, and ΔFosB) or immunohistochemistry (BDNF, trkB, Arc, and c-Fos), in the hippocampus of male Roman high (RHA) and low avoidance (RLA) rats, two psychogenetically selected rat lines that display marked differences in sexual behavior (RHA rats exhibit higher sexual motivation and better copulatory performance than RLA rats). Both methods showed (with some differences) that sexual activity modifies the expression levels of these markers in the hippocampus of Roman rats depending on: (i) the level of sexual experience, that is, changes were usually more evident in sexually naïve than in experienced rats; (ii) the hippocampal partition, that is, BDNF and Arc increased in the dorsal but tended to decrease in the ventral hippocampus; (iii) the marker considered, that is, in sexually experienced animals BDNF, c-Fos, and Arc levels were similar to those of controls, while ΔFosB levels increased; and (iv) the rat line, that is, changes were usually larger in RHA than RLA rats. These findings resemble those of early studies in RHA and RLA rats showing that sexual activity influences the expression of these markers in the nucleus accumbens, medial prefrontal cortex, and ventral tegmental area, and show for the first time that also in the hippocampus sexual activity induces neural activation and plasticity, events that occur mainly during the first phase of the acquisition of sexual experience and depend on the genotypic/phenotypic characteristics of the animals.

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

Cited by 20 publications

References 375 publications

Contribution of the Roman rat lines/strains to personality neuroscience: neurobehavioral modeling of internalizing/externalizing psychopathologies

Contribution of the Roman rat lines/strains to personality neuroscience: neurobehavioral modeling of internalizing/externalizing psychopathologies

Neonatal olfactory bulbectomy induces anxiety‐related behavior and modifies dopaminergic receptor expression in post‐pubertal rats

Neuroplastic changes inc‐Fos,ΔFosB,BDNF,trkB, and Arc expression in the hippocampus of male Roman rats: differential effects of sexual activity

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