Neonatal handling enduringly decreases anxiety and stress responses and reduces hippocampus and amygdala volume in a genetic model of differential anxiety: Behavioral-volumetric associations in the Roman rat strains

Río-Álamos, Cristóbal; Oliveras, Ignasi; Piludu, Marco; Gerbolés, Cristina; Cañete, Toni; Blázquez, Gloria; Lope–Piedrafita, Silvia; Martínez-Membrives, Esther; Torrubia, Rafael; Tobeña, Adolf; Fernández-Teruel, Alberto

doi:10.1016/j.euroneuro.2016.12.003

Cited by 31 publications

(27 citation statements)

References 57 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%

“…This finding, together with the increased amygdala volume in RLA rats (see Fig. 3a), is consistent with previous results of strainrelated differential stress sensitivity and amygdala volume and function [49,52].…”

Section: Nac and Amygdala Activation During Ppi In The Roman And Hs Ratssupporting

confidence: 93%

“…Structural magnetic resonance imaging (MRI) Settings, parameters and brain region analyses were conducted as previously described [52]. Briefly, we obtained 35 coronal T2-weighted fast spin-echo images from the olfactory bulb to the cerebellum, which allowed us to manually count pixels of the whole brain, mPFC (bregma: from 3.72 to 2.52 mm), Cg (bregma: from 3.72 to −1.56 mm), NAc (including shell and core subregions, bregma: from 2.52 to 0.84 mm), HPC (including dorsal and ventral parts, bregma: from −2.40 to −5.52 mm), dorsal striatum (bregma: from 2.28 to 0.96 mm), and amygdala (bregma: from −1.20 to −5.04 mm).…”

Section: Prepulse Inhibition (Ppi) Ppi Was Conducted In Four Sound Atmentioning

confidence: 99%

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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%

Section: Nac and Amygdala Activation During Ppi In The Roman And Hs Ratssupporting

confidence: 93%

Section: Prepulse Inhibition (Ppi) Ppi Was Conducted In Four Sound Atmentioning

confidence: 99%

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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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“…These rats are bidirectionally selected and bred for their rapid (RHA) vs. extremely poor (RLA) ability to acquire the two-way active avoidance response in a shuttle box. More than four decades of research have characterized RHA rats as less fearful, anxious and stress-sensitive than their RLA counterparts (Steimer and Driscoll, 2003; Driscoll et al, 2009; Río-Álamos et al, 2017a,b). 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).…”

Section: Introductionmentioning

confidence: 99%

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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“…With a few exceptions (Poltyrev & Weinstock, 1999; Río-Ȧlamos et al, 2015; Río-Álamos et al, 2017; Skripuletz, Kruschinski, Pabst, von Hörsten, & Stephan, 2010; Stephan, Helfritz, Pabst, & von Horsten, 2002), most studies looking at the consequences of early postnatal manipulations have assessed these effects in a single strain of rat. In order to further examine the dynamic interplay likely to be occurring between early postnatal experiences and genetic background, the present study assessed the effects of neonatal handling on play in the inbred F344 and LEW strains.…”

Section: Discussionmentioning

confidence: 99%

Effects of neonatal handling on play and anxiety in F344 and Lewis rats

Siviy

2018

Developmental Psychobiology

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Play is an important part of normal childhood development and seen in many mammals, including rats. To better understand the interplay between genotype and postnatal experiences, the effects of neonatal handling on play were assessed in Lewis (LEW) and Fischer 344 (F344) rats. Handled litters experienced brief periods of separation during the first two postnatal weeks. F344 rats were less likely to direct nape contacts toward an untreated Sprague-Dawley (SD) partner and less likely to rotate to a supine position in response to a nape contact. When compared to rats from control litters, handled LEW, and F344 rats were more likely to respond to nape contacts with complete rotations, suggesting that handling increased playful responsiveness to a comparable extent in both strains. SD rats paired with handled inbred rats had more nape contacts than those paired with non-handled rats. While handled LEW rats also tended to direct more nape contacts to the SD partner than non-handled LEW rats there was no difference between handled and non-handled F344 rats. These results could not be readily explained by handling-induced changes in either maternal care or anxiety. These data suggest that the behavioral consequences of neonatal handling may not depend to a great extent on the genetic platform that these manipulations are acting on. These data also suggest that the ability to maintain the ebb and flow between playful solicitation and playful responsiveness may be compromised in F344 rats and may contribute to the lower levels of play in this strain.

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Neonatal handling enduringly decreases anxiety and stress responses and reduces hippocampus and amygdala volume in a genetic model of differential anxiety: Behavioral-volumetric associations in the Roman rat strains

Cited by 31 publications

References 57 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

Effects of neonatal handling on play and anxiety in F344 and Lewis rats

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