Volumetric brain differences between the Roman rat strains: Neonatal handling effects, sensorimotor gating and working memory

Río-Álamos, Cristóbal; Piludu, Marco; Gerbolés, Cristina; Barroso, Didac; Oliveras, Ignasi; Sánchez-González, Ana; Cañete, Toni; Tapias-Espinosa, Carles; Sampedro-Viana, Daniel; Torrubia, Rafael; Tobeña, Adolf; Fernández-Teruel, Alberto

doi:10.1016/j.bbr.2018.12.033

Cited by 38 publications

(35 citation statements)

References 86 publications

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“…Regarding the MRI results, study 2 revealed that RHA rats had lower "% volume" of the mPFC and the HPC than the RLAs. These findings agree with previous evidence showing decreased volume of both areas and reduced PPI in RHA compared with RLA rats, as well as a significant positive correlation between HPC volume and PPI [52,61]. In keeping with that, in the present study 4, the HS Low-PPI group had lower mPFC and HPC volumes than the Medium-PPI and High-PPI groups.…”

Section: Discussionsupporting

confidence: 94%

Schizophrenia-like reduced sensorimotor gating in intact inbred and outbred rats is associated with decreased medial prefrontal cortex activity and volume

Tapias-Espinosa

Río-Álamos

Sánchez-González

et al. 2019

Neuropsychopharmacol.

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Prepulse inhibition (PPI) of startle response is a measure of sensorimotor gating that is impaired in schizophrenia and in many other clinical conditions. Rat models using pharmacological or surgical strategies reveal that PPI is modulated by the cortico-striatalpallido-thalamic (CSPT) circuit. Here, we explore whether spontaneous variation in PPI in intact inbred and outbred rats is associated with functional and structural differences in the CSPT circuit. Inbred Roman High-(RHA) and Low-avoidance (RLA) and outbred heterogeneous stock (HS) rats were assessed for PPI, brain activity, and brain volume. Brain activity was assessed by c-Fos expression and brain volume by magnetic resonance imaging. Relevant structures of the CSPT circuit were evaluated, such as the medial prefrontal cortex (mPFC), cingulate cortex, hippocampus (HPC), amygdala, nucleus accumbens (NAc), and dorsal striatum. RHA showed lower PPI than RLA rats, while HS rats were stratified by their PPI levels in three groups. Reduced PPI was accompanied by decreased mPFC activity in Roman and HS rats and increased NAc shell activity in HS rats. Low PPI was also associated with decreased mPFC and HPC volumes in Roman and HS rats. This study reports a consistent relationship between decreased function and volume of the mPFC and spontaneous low-PPI levels in inbred and outbred intact rats. Moreover, our findings suggest that, apart from a hypoactive and smaller mPFC, a hyperactive NAc and smaller HPC may underlie reduced PPI levels. Our results support the notion that sensorimotor gating is modulated by forebrain structures and highlight the importance of the mPFC in its regulation.

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Section: Discussionsupporting

confidence: 94%

Schizophrenia-like reduced sensorimotor gating in intact inbred and outbred rats is associated with decreased medial prefrontal cortex activity and volume

Tapias-Espinosa

Río-Álamos

Sánchez-González

et al. 2019

Neuropsychopharmacol.

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“…In line with these strain-related differences in LI, we have shown in a series of studies that RHA rats display clear and consistent deficits of PPI of the acoustic startle response compared with RLAs (Del Rio et al, 2014; Oliveras et al, 2015, 2016, 2017; Río-Alamos et al, 2015; Río-Álamos et al, 2017a,b, 2019; Tapias-Espinosa et al, 2018, 2019) and that PPI deficits predict spatial working memory impairments (Oliveras et al, 2015). Altogether, the above mentioned cognitive and attentional profiles of RHA vs. RLA rats suggest that the former may represent a model of schizophrenia-relevant features.…”

Section: Rha Rats As a Model Of Deficits In Attentional Processes Comentioning

confidence: 52%

“…This difference in the sensitivity to changes in environmental conditions critically influences behavioral flexibility, which is generally higher in subjects characterized by a reactive coping style. For example, proactive coping RHA rats -that are also impulsive- are impaired at solving a spatial reversal learning task compared with their reactive coping RLA counterparts (Escorihuela et al, 1995; Río-Álamos et al, 2019). Thus, proactive coping styles in experimental animals and in humans are frequently positively associated with impulsivity, behavioral (cognitive) inflexibility and also with deficits in behavioral inhibition (for a review, see Coppens et al, 2010).…”

Section: Coping Style Behavioral Flexibility Behavioral Inhibition mentioning

confidence: 99%

“…Remarkably, compared with RLAs, RHA rats display an impulsive phenotype, as shown by their response profiles in the delayed response latency 20 (DRL-20), schedule-induced polydipsia, and 5-choice serial reaction time (5CSRT) tasks (Zeier et al, 1978; Moreno et al, 2010; Merchán et al, 2019; see “The Roman Rats: A Genetic Model of Differential Anxiety, Novelty Seeking, Impulsivity, Attention Deficits and Associated Traits” section). Moreover, relative to RLAs, RHA rats display several impairments in schizophrenia-relevant phenotypes, such as prepulse inhibition (PPI; Oliveras et al, 2015; Río-Álamos et al, 2019), latent inhibition (LI; Fernández-Teruel et al, 2006), spatial working memory (Oliveras et al, 2015) and reversal learning (Río-Álamos et al, 2019) as well as a trend towards a reduction of some types of social behavior (Coppens et al, 2012; Del Rio et al, 2014; see “RHA Rats as a Model of Deficits in Attentional Processes, Cognitive Impairments and Other Features Relevant for Schizophrenia Research” section). These behavioral profiles are consistent with findings of a reduced volume and function of the medial prefrontal cortex (mPFCx), hippocampus (HC) and amygdala (AMY) of RHA vs. RLA rats (Río-Álamos et al, 2017a, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, relative to RLAs, RHA rats display several impairments in schizophrenia-relevant phenotypes, such as prepulse inhibition (PPI; Oliveras et al, 2015; Río-Álamos et al, 2019), latent inhibition (LI; Fernández-Teruel et al, 2006), spatial working memory (Oliveras et al, 2015) and reversal learning (Río-Álamos et al, 2019) as well as a trend towards a reduction of some types of social behavior (Coppens et al, 2012; Del Rio et al, 2014; see “RHA Rats as a Model of Deficits in Attentional Processes, Cognitive Impairments and Other Features Relevant for Schizophrenia Research” section). These behavioral profiles are consistent with findings of a reduced volume and function of the medial prefrontal cortex (mPFCx), hippocampus (HC) and amygdala (AMY) of RHA vs. RLA rats (Río-Álamos et al, 2017a, 2019). Finally, as it would be expected from a model with translational value, compared with RLAs, RHA rats also show more intense behavioral sensitization following the repeated administration of psychostimulants (Corda et al, 2005; Giorgi et al, 2005a, 2007) and enhanced vulnerability to drug abuse/addiction (Fattore et al, 2009), which are associated with a more robust mesolimbic dopaminergic tone (Giorgi et al, 1997, 2003, 2005b; Piras et al, 2003; Lecca et al, 2004; see “The Roman Rats as a Genetic Model of Vulnerability to Drug Addiction” section).…”

Section: Introductionmentioning

confidence: 99%

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A Genetic Model of Impulsivity, Vulnerability to Drug Abuse and Schizophrenia-Relevant Symptoms With Translational Potential: The Roman High- vs. Low-Avoidance Rats

Giorgi

Corda

Fernandez-Teruel

2019

Front. Behav. Neurosci.

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The bidirectional selective breeding of Roman high- (RHA) and low-avoidance (RLA) rats for respectively rapid vs. poor acquisition of active avoidant behavior has generated two lines/strains that differ markedly in terms of emotional reactivity, with RHA rats being less fearful than their RLA counterparts. Many other behavioral traits have been segregated along the selection procedure; thus, compared with their RLA counterparts, RHA rats behave as proactive copers in the face of aversive conditions, display a robust sensation/novelty seeking (SNS) profile, and show high impulsivity and an innate preference for natural and drug rewards. Impulsivity is a multifaceted behavioral trait and is generally defined as a tendency to express actions that are poorly conceived, premature, highly risky or inappropriate to the situation, that frequently lead to unpleasant consequences. High levels of impulsivity are associated with several neuropsychiatric conditions including attention-deficit hyperactivity disorder, obsessive-compulsive disorder, schizophrenia, and drug addiction. Herein, we review the behavioral and neurochemical differences between RHA and RLA rats and survey evidence that RHA rats represent a valid genetic model, with face, construct, and predictive validity, to investigate the neural underpinnings of behavioral disinhibition, novelty seeking, impulsivity, vulnerability to drug addiction as well as deficits in attentional processes, cognitive impairments and other schizophrenia-relevant traits.

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Activation of the mPFC‐NAc Pathway Reduces Motor Impulsivity but Does Not Affect Risk‐Related Decision‐Making in Innately High‐Impulsive Male Rats

Arrondeau,

Urueña‐Méndez,

Marchessaux

et al. 2024

J of Neuroscience Research

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Attention‐deficit/hyperactivity disorder (ADHD) and substance use disorders (SUD) are characterized by exacerbated motor and risk‐related impulsivities, which are associated with decreased cortical activity. In rodents, the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) have been separately implicated in impulsive behaviors, but studies on the specific role of the mPFC‐NAc pathway in these behaviors are limited. Here, we investigated whether heightened impulsive behaviors are associated with reduced mPFC activity in rodents and determined the involvement of the mPFC‐NAc pathway in motor and risk‐related impulsivities. We used the Roman High‐ (RHA) and Low‐Avoidance (RLA) rat lines, which display divergent phenotypes in impulsivity. To investigate alterations in cortical activity in relation to impulsivity, regional brain glucose metabolism was measured using positron emission tomography and [18F]‐fluorodeoxyglucose ([18F]FDG). Using chemogenetics, the activity of the mPFC‐NAc pathway was either selectively activated in high‐impulsive RHA rats or inhibited in low‐impulsive RLA rats, and the effects of these manipulations on motor and risk‐related impulsivity were concurrently assessed using the rat gambling task. We showed that basal [18F]FDG uptake was lower in the mPFC and NAc of RHA compared to RLA rats. Activation of the mPFC‐NAc pathway in RHA rats reduced motor impulsivity, without affecting risk‐related decision‐making. Conversely, inhibition of the mPFC‐NAc pathway had no effect in RLA rats. Our results suggest that the mPFC‐NAc pathway controls motor impulsivity, but has limited involvement in risk‐related decision‐making in our current model. Our findings suggest that reducing fronto‐striatal activity may help attenuate motor impulsivity in patients with impulse control dysregulation.

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Volumetric brain differences between the Roman rat strains: Neonatal handling effects, sensorimotor gating and working memory

Cited by 38 publications

References 86 publications

Schizophrenia-like reduced sensorimotor gating in intact inbred and outbred rats is associated with decreased medial prefrontal cortex activity and volume

Schizophrenia-like reduced sensorimotor gating in intact inbred and outbred rats is associated with decreased medial prefrontal cortex activity and volume

A Genetic Model of Impulsivity, Vulnerability to Drug Abuse and Schizophrenia-Relevant Symptoms With Translational Potential: The Roman High- vs. Low-Avoidance Rats

Activation of the mPFC‐NAc Pathway Reduces Motor Impulsivity but Does Not Affect Risk‐Related Decision‐Making in Innately High‐Impulsive Male Rats

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