Decreased social interaction in the RHA rat model of schizophrenia-relevant features: Modulation by neonatal handling

Sampedro-Viana, Daniel; Cañete, Toni; Sanna, Francesco; Soley, Bernat; Giorgi, Osvaldo; Corda, Maria Giuseppa; Torrecilla, Pilar; Oliveras, Ignasi; Tapias-Espinosa, Carles; Río-Álamos, Cristóbal; Sánchez-González, Ana; Tobeña, Adolf; Fernández-Teruel, Alberto

doi:10.1016/j.beproc.2021.104397

Cited by 13 publications

(5 citation statements)

References 49 publications

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“…A considerable number of pharmacological studies, with anxiolytic, antidepressant and anxiogenic drugs, or with psychostimulants, pro-psychotic and antipsychotic compounds, among others, have been carried out in the Roman rat lines/strains (e.g., Oliveras et al, 2017; Sampedro-Viana et al, 2023; see reviews by Fernández-Teruel et al, 2021, and Giorgi et al, 2019, and further references). While these studies globally give support to the predictive validity of RLAs as a model of anxiety (i.e., threat sensitivity) and RHAs as a model of schizophrenia-relevant phenotypes and drug-addiction vulnerability (i.e., reward sensitivity), much more psycho- and neuro-pharmacological research is still necessary.…”

Section: What More Can the Roman Rats Tell Us About Personality Neuro...mentioning

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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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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Section: What More Can the Roman Rats Tell Us About Personality Neuro...mentioning

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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“…The signaling system regulates feeding and social behaviors 50 . These results suggested that the deletion of the Tet1 gene in uences mPFC neuronal growth, thereby affecting social behaviors and PPI, which may have a connection with schizophrenia 51,52 .…”

Section: Discussionmentioning

confidence: 88%

Deletion of Tet1 in Mice with Impaired Prefrontal Cortex Functions by Activating the NGF/TrkA Signaling Pathway

Gao

2023

Preprint

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Tet1 (ten-eleven translocation methylcytosine dioxygenase 1) is the enzyme methylcytosine dioxygenase of DNA demethylation in the nervous system. Tet1 controls and mediates gene transcription, memory formation, and extinction. However, little is known about Tet1 in prefrontal cortex (PFC) functions especially in the medial prefrontal cortex (mPFC), which controls cortex flexibility and emotional reactivity in the CNS. This study conducted behavioral tests including an open field test, sociability and social novelty preference tests, social dominance, and prepulse inhibition test to examine brain functions, especially PFC functions after the deletion of Tet1. The mPFC from Tet1 KO mice and WT adult mice was analyzed using qRT-PCR to assess neuron growth-related genes, including Gsk3β, Pi3k, Crx4, Fgfr1, Fgfr2, Egfr, Dbn1, Akt2, Vegf, Vegfr, and Akt3. Subsequently, primary PFC neuronal cells were administered shTet1 to knockdown the Tet1 gene and function. We found that the deletion of Tet1 in the mouse brains impaired social interaction, novelty, and prepulse inhibition (PPI) in the mice. Knockdown of the Tet1 gene influenced the growth and complexity of neurons. The increase in Ngf and Bdnf by Western blotting were found in Tet1 deficient mice. The results support and complement the view that Tet1 deficiency may be related to schizophrenia.

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“…The Roman Low Avoidance (RLA) strain has consistently shown high anxiety compared to the Roman High Avoidance (RHA) animals ( Giorgi et al, 2019 ). However, after neonatal handling, social interaction increases in males of both strains in parallel with their decreased anxiety ( Sampedro-Viana et al, 2021 ). The authors of that study argue that the effects of neonatal handling on social interaction seem to be independent from the reduction of anxiety.…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Behavioral Response to Early Adolescent Stress in the Genetically More Stress-Reactive Wistar Kyoto More Immobile, and Its Nearly Isogenic Wistar Kyoto Less Immobile Control Strain

Kim

Gacek

Mocchi

et al. 2021

Front. Behav. Neurosci.

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Genetic predisposition and environmental stress are known etiologies of stress-related psychiatric disorders. Environmental stress during adolescence is assumed to be particularly detrimental for adult affective behaviors. To investigate how genetic stress-reactivity differences modify the effects of stress during adolescence on adult affective behaviors we employed two inbred strains with differing stress reactivity. The Wistar Kyoto More Immobile (WMI) rat strain show increased stress-reactivity and despair-like behaviors as well as passive coping compared to the nearly isogenic control strain, the Wistar Kyoto Less Immobile (WLI). Males and females of these strains were exposed to contextual fear conditioning (CFC) during early adolescence (EA), between 32 and 34 postnatal days (PND), and were tested for the consequences of this mild EA stress in adulthood. Early adolescent stress significantly decreased anxiety-like behavior, measured in the open field test (OFT) and increased social interaction and recognition in adult males of both strains compared to controls. In contrast, no significant effects of EA stress were observed in adult females in these behaviors. Both males and females of the genetically less stress-reactive WLI strain showed significantly increased immobility in the forced swim test (FST) after EA stress compared to controls. In contrast, immobility was significantly attenuated by EA stress in adult WMI females compared to controls. Transcriptomic changes of the glucocorticoid receptor (Nr3c1, GR) and the brain-derived neurotrophic factor (Bdnf) illuminate primarily strain and stress-dependent changes, respectively, in the prefrontal cortex and hippocampus of adults. These results suggest that contrary to expectations, limited adolescent stress is beneficial to males thru decreasing anxiety and enhancing social behaviors, and to the stress more-reactive WMI females by way of decreasing passive coping.

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Decreased social interaction in the RHA rat model of schizophrenia-relevant features: Modulation by neonatal handling

Cited by 13 publications

References 49 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

Deletion of Tet1 in Mice with Impaired Prefrontal Cortex Functions by Activating the NGF/TrkA Signaling Pathway

Sex-Specific Behavioral Response to Early Adolescent Stress in the Genetically More Stress-Reactive Wistar Kyoto More Immobile, and Its Nearly Isogenic Wistar Kyoto Less Immobile Control Strain

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