Roman Rat Strains Research Articles

Contrasting Effects of Oxytocin on MK801-Induced Social and Non-Social Behavior Impairment and Hyperactivity in a Genetic Rat Model of Schizophrenia-Linked Features.

Social withdrawal in rodents is a measure of asociality, an important negative symptom of schizophrenia. The Roman high- (RHA) and low-avoidance (RLA) rat strains have been reported to exhibit differential profiles in schizophrenia-relevant behavioral phenotypes. This investigation was focused on the study of social and non-social behavior of these two rat strains following acute administration of dizocilpine (MK801, an NMDA receptor antagonist), a pharmacological model of schizophrenia-like features used to produce asociality and hyperactivity. Also, since oxytocin (OXT) has been proposed as a natural antipsychotic and a potential adjunctive therapy for social deficits in schizophrenia, we have evaluated the effects of OXT administration and its ability to reverse the MK801-impairing effects on social and non-social behavior and MK801-induced hyperactivity. MK801 administration produced hyperlocomotion and a decrease in social and non-social behavior in both rat strains, but these drug effects were clearly more marked in RHA rats. OXT (0.04 mg/kg and 0.2 mg/kg) attenuated MK801-induced hyperlocomotion in both rat strains, although this effect was more marked in RHA rats. The MK801-decreasing effect on exploration of the "social hole" was moderately but significantly attenuated only in RLA rats. This study is the first to demonstrate the differential effects of OXT on MK801-induced impairments in the two Roman rat strains, providing some support for the potential therapeutic effects of OXT against schizophrenia-like symptoms, including both a positive-like symptom (i.e., MK801-induced hyperlocomotion) and a negative-like symptom (i.e., MK801 decrease in social behavior), while highlighting the importance of the genetic background (i.e., the rat strain) in influencing the effects of both MK801 and oxytocin.

Schizophrenia-relevant social, attentional and cognitive traits in female RHA vs. RLA rats: effects of neonatal handling

The Roman high- (RHA) and low-avoidance (RLA) rats were bidirectionally selected and bred for, respectively, their rapid vs. extremely poor acquisition in the two-way active avoidance task. Consistent between-strain neurobehavioural differences have been found in anxiety- and stress-linked traits, as well as in schizophrenia-related phenotypes. RLAs display enhanced anxious- and stress-related phenotypes, whereas RHA rats show impulsivity, hyperactivity and attention/cognition-related impairments. Many of these typical behavioural phenotypes have been reported to be positively modulated by environmental treatments such as neonatal handling (NH). However, most studies on the Roman rat strains have been carried out in males. Thus, the present study for the first time focused on the joint evaluation of differences in novel object exploration (NOE), social interaction (SI), prepulse inhibition of the startle response (PPI), and cognitive performance and flexibility in various spatial tasks (using the Morris water maze, MWM) in females of both Roman rat strains. We also aimed at evaluating the long-lasting effects of NH treatment on the RHA vs. RLA profiles in these tests/tasks. Results show that anxiety-related behavior, as measured by the NOE test and self-grooming in the SI test, was increased in RLA rats, and dramatically reduced by NH. In the SI test RLA rats displayed diminished social interaction, which was rescued by NH. RHA females exhibited a deficit of PPI, which was not affected by NH. Spatial tasks in the MWM showed impairments of working memory, reference learning/memory and spatial reversal learning (i.e., cognitive flexibility) in RHA females. Spatial reference learning and cognitive flexibility (i.e., reversal task) showed some improvement in rats (mainly in RHAs) that had received NH during the first three weeks of life. With the exception of the SI test, the pattern of differences between female RHA vs. RLA profiles was overall consistent with what has previously been found in males of both strains, and NH treatment was able to enduringly improve some emotion-related and (spatial) cognitive outcomes in both strains.

C-Fos expression after neonatal handling in social brain regions: Distinctive profile of RHA-rat schizophrenia model on a social preference test

Neonatal handling (NH) is an environmental manipulation that induces long-lasting changes in behavioural, neuroendocrine, and neuroanatomical processes in rodents. We have previously reported that NH treatment increases social interaction preference in an animal model of schizophrenia-relevant features, the Roman high-avoidance (RHA) rats. The present study was aimed at evaluating whether the increase of social behaviour/preference due to NH treatment in RHA rats is associated with differences in c-Fos expression levels in some of the brain areas that integrate the “social brain”. To this aim, we evaluated the performance of adult male rats from both Roman rat strains (RHA vs. RLA –Roman low-avoidance- rats), either untreated (control) or treated with NH (administered during the first 21 days of life) in a social interaction task. For the analyses of c-Fos activation untreated and NH-treated animals were divided into three different experimental conditions: undisturbed home cage controls (HC); rats exposed to the testing set-up context (CTX); and rats exposed to a social interaction (SI) test. It was found that, compared with their RLA counterparts, NH treatment increased social behaviour in RHA rats, and also specifically enhanced c-Fos expression in RHA rats tested for SI in some brain areas related to social behaviour, i.e. the infralimbic cortex (IL) and the medial posterodorsal amygdala (MePD) regions.

Neurobiology of sensorimotor gating deficits in the Roman rat strains: Studies of c-Fos expression and COMT activity

The present study was aimed at evaluating whether the differences between the Roman high- (RHA) and low-avoidance (RLA) rat strains in novelty-induced behavioural inhibition/disinhibition, sensorimotor gating (i.e., prepulse inhibition, PPI) and spatial learning/memory parallel differences in the volume of brain areas related to those behavioural phenotypes. To this aim, we conducted two experiments. In Experiment 1, we evaluated the performance of adult rats from both strains, either untreated (controls) or treated with neonatal handling (NH; administered during the first 21 days of life), in a novel object exploration test (NOE), in the elevated zero-maze test (ZM) of anxiety, and in a PPI test; moreover, magnetic resonance imaging (MRI) was used to measure the volume of limbic and cortical brain regions (amygdala -Am-, hippocampus -Hc-, striatum -St-, medial prefrontal cortex -mPFc-, anterior cingulate cortex -ACC-, nucleus accumbens -NAc-) and lateral ventricles -LV-. In Experiment 2, adult rats neonatally exposed to NH and their naïve controls were submitted to the NOE and PPI tests, and to several spatial learning/memory tasks using the Morris water maze. It was found that, compared with their RLA counterparts, RHA rats show increased exploration of the novel object in the NOE test, lowered anxiety in the ZM and impaired PPI, whereas RLAs display better spatial reference learning and memory and better cognitive flexibility in a reversal task. Furthermore, MRI measurements revealed that the volume of Hc, Am and mPFc is larger in RLA vs. RHA rats, whereas the latter have dramatically enlarged lateral ventricles. NH treatment markedly enhanced exploration in the NOE test in RLA rats, improved PPI in RHA rats but impaired it in their RLA counterparts, and produced beneficial effects on spatial working memory mainly in RHA rats. Finally, exposure to NH decreased the volume of Hc and Am in the RLA strain. The results are discussed in terms of the possible relationships between strain-related volumetric brain differences and the behavioral (anxiety-related and schizophrenia-relevant) traits that distinguish RHA from RLA rats, and highlighting the finding that, in RLA rats, NH is for the first time shown to enduringly reduce the volume of Hc and Am in parallel to the decrease of anxiety and the impairment of sensorimotor gating.

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

The present study was aimed at evaluating whether the differences between the Roman high- (RHA) and low-avoidance (RLA) rat strains in novelty-induced behavioural inhibition/disinhibition, sensorimotor gating (i.e., prepulse inhibition, PPI) and spatial learning/memory parallel differences in the volume of brain areas related to those behavioural phenotypes. To this aim, we conducted two experiments. In Experiment 1, we evaluated the performance of adult rats from both strains, either untreated (controls) or treated with neonatal handling (NH; administered during the first 21 days of life), in a novel object exploration test (NOE), in the elevated zero-maze test (ZM) of anxiety, and in a PPI test; moreover, magnetic resonance imaging (MRI) was used to measure the volume of limbic and cortical brain regions (amygdala -Am-, hippocampus -Hc-, striatum -St-, medial prefrontal cortex -mPFc-, anterior cingulate cortex -ACC-, nucleus accumbens -NAc-) and lateral ventricles -LV-. In Experiment 2, adult rats neonatally exposed to NH and their naïve controls were submitted to the NOE and PPI tests, and to several spatial learning/memory tasks using the Morris water maze. It was found that, compared with their RLA counterparts, RHA rats show increased exploration of the novel object in the NOE test, lowered anxiety in the ZM and impaired PPI, whereas RLAs display better spatial reference learning and memory and better cognitive flexibility in a reversal task. Furthermore, MRI measurements revealed that the volume of Hc, Am and mPFc is larger in RLA vs. RHA rats, whereas the latter have dramatically enlarged lateral ventricles. NH treatment markedly enhanced exploration in the NOE test in RLA rats, improved PPI in RHA rats but impaired it in their RLA counterparts, and produced beneficial effects on spatial working memory mainly in RHA rats. Finally, exposure to NH decreased the volume of Hc and Am in the RLA strain. The results are discussed in terms of the possible relationships between strain-related volumetric brain differences and the behavioral (anxiety-related and schizophrenia-relevant) traits that distinguish RHA from RLA rats, and highlighting the finding that, in RLA rats, NH is for the first time shown to enduringly reduce the volume of Hc and Am in parallel to the decrease of anxiety and the impairment of sensorimotor gating.

Increased exploratory activity in rats with deficient sensorimotor gating: a study of schizophrenia-relevant symptoms with genetically heterogeneous NIH-HS and Roman rat strains

Schizophrenia involves positive, negative and cognitive symptoms, as well as comorbidity with anxiety and obsessive-compulsive disorder. Prepulse inhibition (PPI) of the startle response is a measure of sensorimotor gating that is impaired in schizophrenia and animal models of the disease. Remarkably, impaired PPI has been related to other schizophrenia-like features in rodent models, such as cognitive deficits and hyperactivity. However, it remains to be investigated whether deficient PPI and increased exploratory activity are associated in genetically heterogeneous (outbred) naïve animals. This study was undertaken to evaluate the relationships among PPI and other schizophrenia-related symptoms, such as augmented exploratory activity, anxiety and compulsivity in the genetically heterogeneous (outbred) NIH-HS rat stock (HS) and in the genetically-selected inbred Roman High-Avoidance (RHA) and Low-avoidance (RLA) rats. Animals underwent the following tests: open-field (exploratory activity), elevated zero-maze (anxiety-like behavior), marble burying (compulsive-like behavior), and PPI. Three groups of HS rats were formed according to their PPI scores, i.e. Low-PPI, Medium-PPI and High-PPI. The HS Low-PPI group displayed higher exploratory activity in the open-field than the HS Medium-PPI and HS High-PPI groups. Likewise, compared with their RLA counterparts, RHA rats exhibited lower PPI and more intense exploratory activity in the open-field test. Correlational and factorial analyses of the whole HS sample and the RHA/RLA data globally corroborated the results of the PPI-stratified HS subgroups. These data suggest that such a consistent association between impaired PPI and increased exploratory activity in outbred HS and inbred RHA/RLA rats is a relevant parameter that must be taken into account when modeling clusters of schizophrenia-relevant symptoms.

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

The hippocampus and amygdala have been proposed as key neural structures related to anxiety. A more active hippocampus/amygdala system has been related to greater anxious responses in situations involving conflict/novelty. The Roman Low- (RLA) and High-avoidance (RHA) rat lines/strains constitute a genetic model of differential anxiety. Relative to RHA rats, RLA rats exhibit enhanced anxiety/fearfulness, augmented hippocampal/amygdala c-Fos expression following exposure to novelty/conflict, increased hippocampal neuronal density and higher endocrine responses to stress. Neonatal handling (NH) is an environmental treatment with long-lasting anxiety/stress-reducing effects in rodents. Since hippocampus and amygdala volume are supposed to be related to anxiety/fear, we hypothesized a greater volume of both areas in RLA than in RHA rats, as well as that NH treatment would reduce anxiety and the volume of both structures, in particular in the RLA strain. Adult untreated and NH-treated RHA and RLA rats were tested for anxiety, sensorimotor gating (PPI), stress-induced corticosterone and prolactin responses, two-way active avoidance acquisition and in vivo 7 T 1H-Magnetic resonance image. As expected, untreated RLA rats showed higher anxiety and post-stress hormone responses, as well as greater hippocampus and amygdala volumes than untreated RHA rats. NH decreased anxiety/stress responses, especially in RLA rats, and significantly reduced hippocampus and amygdala volumes in this strain. Dorsal striatum volume was not different between the strains nor it was affected by NH. Finally, there were positive associations (as shown by correlations, factor analysis and multiple regression) between anxiety and PPI and hippocampus/amygdala volumes.

Transfer across reward devaluation tasks in inbred Roman rat strains

Emotional counterconditioning resulting from pairings between a state of frustration and food reward explains transfer across situations involving reward omission. This experiment explored the hypothesis that a similar emotional counterconditioning mechanism is also involved in recovery from reward devaluation. Inbred Roman high- and low-avoidance rat strains (RHA-I and RLA-I) were trained in consummatory and instrumental successive negative contrast tasks (cSNC and iSNC) in counterbalanced order. RLA-I rats have consistently shown high levels of anxiety in a variety of situations, relative to RHA-I rats. Therefore, a stronger evidence of transfer was expected in RLA-I rats than in RHA-I rats. Whereas both strains showed the effects in the original training phase, only RLA-I rats benefitted from prior exposure to one reward devaluation task. The transfer was positive and symmetrical (i.e., exposure to one SNC task attenuated the second effect). RHA-I rats produced no evidence of transfer. The results suggest that emotional counterconditioning is involved in recovery from reward devaluation tasks. Despite extensive psychogenetic selection for low-avoidance/high-anxiety behavior, RLA-I rats showed the ability to develop resilience as a function of prior experience.

Spatial learning in the genetically heterogeneous NIH-HS rat stock and RLA-I/RHA-I rats: Revisiting the relationship with unconditioned and conditioned anxiety

To characterize learning/memory profiles for the first time in the genetically heterogeneous NIH-HS rat stock, and to examine whether these are associated with anxiety, we evaluated NIH-HS rats for spatial learning/memory in the Morris water maze (MWM) and in the following anxiety/fear tests: the elevated zero-maze (ZM; unconditioned anxiety), a context-conditioned fear test and the acquisition of two-way active avoidance (conditioned anxiety). NIH-HS rats were compared with the Roman High- (RHA-I) and Low-Avoidance (RLA-I) rat strains, given the well-known differences between the Roman strains/lines in anxiety-related behavior and in spatial learning/memory. The results show that: (i) As expected, RLA-I rats were more anxious in the ZM test, displayed more frequent context-conditioned freezing episodes and fewer avoidances than RHA-I rats. (ii) Scores of NIH-HS rats in these tests/tasks mostly fell in between those of the Roman rat strains, and were usually closer to the values of the RLA-I strain. (iii) Pigmented NIH-HS (only a small part of NIH-HS rats were albino) rats were the best spatial learners and displayed better spatial memory than the other three (RHA-I, RLA-I and NIH-HS albino) groups. (iv) Albino NIH-HS and RLA-I rats also showed better learning/memory than the RHA-I strain. (v) Within the NIH-HS stock, the most anxious rats in the ZM test presented the best learning and/or memory efficiency (regardless of pigmentation). In summary, NIH-HS rats display a high performance in spatial learning/memory tasks and a passive coping strategy when facing conditioned conflict situations. In addition, unconditioned anxiety in NIH-HS rats predicts better spatial learning/memory.

Coping style and stress hormone responses in genetically heterogeneous rats: Comparison with the Roman rat strains

The purpose of the present study was to evaluate for the first time the stress-induced hypothalamus–pituitary–adrenal (HPA), adrenocorticotropic hormone (ACTH), corticosterone and prolactin responses of the National Institutes of Health genetically heterogeneous rat stock (N/Nih-HS rats) in comparison with responses of the relatively high and low stress-prone Roman Low- (RLA-I) and High-Avoidance (RHA-I) rat strains. The same rats were also compared (experiment 1) with respect to their levels of unconditioned anxiety (elevated zero-maze test), novelty-induced exploratory behavior, conditioned fear and two-way active avoidance acquisition. In experiment 2, naive rats from these three strains/stocks were evaluated for “depressive-like” behavior in the forced swimming test. N/Nih-HS and RLA-I rats showed significantly higher post-stress ACTH, corticosterone and prolactin levels than RHA-I rats. N/Nih-HS rats also presented the highest context-conditioned freezing responses, extremely poor two-way avoidance acquisition and very low novelty-induced exploratory behavior. Experiment 2 showed that, compared to RHA-I rats, N/Nih-HS and RLA-I rats displayed significantly less struggling (escape-directed) and increased immobility responses in the forced swimming test. Factor analysis of data from experiment 1 showed associations among behavioral and hormonal responses, with a first factor comprising high loadings of elevated zero-maze variables and lower loadings of conditioned fear, two-way avoidance acquisition and hormonal measures, while a second factor mainly grouped conditioned fear and two-way avoidance acquisition with novelty-induced exploration and post-stress prolactin. Thus, regarding their anxiety/fearfulness, passive coping style, “depressive-like” and stress-induced hormonal responses the N/Nih-HS rats resemble the phenotype profiles of the relatively high-anxious and stress-prone RLA-I rat strain.

Impulsivity characterization in the Roman high- and low-avoidance rat strains: behavioral and neurochemical differences.

The selective breeding of Roman high- (RHA) and low-avoidance (RLA) rats for rapid vs extremely poor acquisition of active avoidance behavior in a shuttle-box has generated two phenotypes with different emotional and motivational profiles. The phenotypic traits of the Roman rat lines/strains (outbred or inbred, respectively) include differences in sensation/novelty seeking, anxiety/fearfulness, stress responsivity, and susceptibility to addictive substances. We designed this study to characterize differences between the inbred RHA-I and RLA-I strains in the impulsivity trait by evaluating different aspects of the multifaceted nature of impulsive behaviors using two different models of impulsivity, the delay-discounting task and five-choice serial reaction time (5-CSRT) task. Previously, rats were evaluated on a schedule-induced polydipsia (SIP) task that has been suggested as a model of obsessive-compulsive disorder. RHA-I rats showed an increased acquisition of the SIP task, higher choice impulsivity in the delay-discounting task, and poor inhibitory control as shown by increased premature responses in the 5-CSRT task. Therefore, RHA-I rats manifested an increased impulsivity phenotype compared with RLA-I rats. Moreover, these differences in impulsivity were associated with basal neurochemical differences in striatum and nucleus accumbens monoamines found between the two strains. These findings characterize the Roman rat strains as a valid model for studying the different aspects of impulsive behavior and for analyzing the mechanisms involved in individual predisposition to impulsivity and its related psychopathologies.

Unlearned anxiety predicts learned fear: A comparison among heterogeneous rats and the Roman rat strains

Anxiety-related behaviors were evaluated across five tests in a sample of 277 rats from a genetically heterogeneous stock (N/Nih-HS rats), derived from an eight-way cross of inbred strains, and compared with the performance of RLA-I (high anxious) and RHA-I (low anxious) rats in the same tests. These tests either evoke unlearned (novel-cage activity (NACT), elevated “zero” maze (ZM), baseline acoustic startle response (BAS)) or learned (fear-potentiated startle (FPS), two-way active-shuttle box-avoidance acquisition (SHAV)) anxious/fearful responses. The results overall showed that unlearned anxiety responses/behaviors were predictive of behavior in learned fear (i.e. fear-potentiated startle) and conflict (i.e. two-way active avoidance acquisition) situations. Moreover, it was found that N/Nih-HS rats either resemble RLA-I rat anxiety/fear scores or fall in between those of the RLA-I (high anxious) and the RHA-I (low anxious) rat strains. An additional regression analysis (of N/Nih-HS rat data) showed significant positive influences of (unlearned) baseline startle response, risk assessment (i.e. stretch-attend) behavior and activity (5 min) in a novel cage on SHAV acquisition, while baseline startle and entries into the open section of the elevated ‘zero’ maze test of anxiety were the main variables influencing FPS. This indicates that startle responses may have a facilitating role in the rat's active responses in the two-way active (shuttlebox) avoidance acquisition. The results of this behavioral evaluation of N/Nih-HS rats show that unconditioned anxiety (e.g. in the ZM test) predicts learned fear-related responses (e.g. FPS and SHAV) to some extent, while a positive association is also observed between BAS and SHAV. These findings are discussed in terms of their potential usefulness for present and future neurobehavioral and genetic studies of fearfulness/anxiety.

Consummatory successive negative and anticipatory contrast effects in inbred Roman rats

Three experiments were designed to study the performance of female inbred Roman High-(RHA-I) and Low-(RLA-I) Avoidance rats in a consummatory task in which successive negative (cSNC) and anticipatory contrast (cANC) effects were induced by changing the concentration of the sucrose solution used as reward. Both RHA-I and RLA-I rats showed a significant suppression of drinking (cSNC) when they were exposed to 32% sucrose in preshift phase and 4% in postshift phase, in comparison to RHA-I and RLA-I control groups always exposed to 4% sucrose (Experiment 1). By contrast, when the preshift–postshift reward discrepancy was reduced from 32-4 to 22-4 in Experiment 2, both strains showed a suppression of fluid intake on the first postshift trial, whereas only the more emotional RLA-I strain maintained this suppression on subsequent days. Finally, no consumption differences were observed between RHA-I and RLA-I rats exposed to brief daily access to 4% sucrose followed by access to 22% sucrose (cANC, Experiment 3). These results suggest that differences between the Roman rat strains in consummatory contrast paradigms can only be observed when the sucrose solution manipulation implies an incentive loss-attenuated emotional situation, but not when it occurs in an anticipatory manner.

Unlearned anxiety predicts learned fear: A comparison among heterogeneous rats and the Roman rat strains

Event Abstract Back to Event Unlearned anxiety predicts learned fear: A comparison among heterogeneous rats and the Roman rat strains Regina Lopez-Aumatell1*, Elia Vicens-Costa1, Esther Martinez-Membrives1, Toni Canete1, Gloria Blazquez1, Adolf Tobena1 and Alberto Fernandez-Teruel1 1 Universitat Autònoma de Barcelona, Spain We present the behavioural phenotyping of a large sample of rats from the National Institutes of Health Genetically Heterogeneous Rat Stock (N/Nih-HS), including males and females, and the comparison of their results with the RLA-I (very anxious) and RHA-I (low anxious) rat strains. Rats were tested in several anxiety tests comprising unlearned fear (like the novel-cage activity, the elevated “zero” maze and the baseline acoustic startle response), as well as learned fear/anxiety responses (fear-potentiated startle and two-way active shuttlebox avoidance). The results overall showed that unlearned anxiety responses/behaviour were predictive of behaviour in learned fear (i.e. fear-potentiated startle) and conflict (i.e. two-way active avoidance acquisition) situations. N/Nih-HS rats either resemble RLA-I rat anxiety/fear scores or fall in between those of the RLA-I (high anxious) and the RHA-I (low anxious) rat strains. Regression analysis of the N/Nih-HS rat data show that unconditioned anxiety predicts learned fear to some extent, and point that startle measures may have a facilitating role in the rat’s active responses in the two-way active (shuttlebox) avoidance acquisition. Acknowledgements:Partially supported by EURATools (European Commission Contract no. LSHG-CT-2005-019015) and the Wellcome Trust (R. L-A). Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Lopez-Aumatell R, Vicens-Costa E, Martinez-Membrives E, Canete T, Blazquez G, Tobena A and Fernandez-Teruel A (2009). Unlearned anxiety predicts learned fear: A comparison among heterogeneous rats and the Roman rat strains. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.221 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Jun 2009; Published Online: 11 Jun 2009. * Correspondence: Regina Lopez-Aumatell, Universitat Autònoma de Barcelona, Bellaterra, Spain, regina.lopez@uab.es Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Regina Lopez-Aumatell Elia Vicens-Costa Esther Martinez-Membrives Toni Canete Gloria Blazquez Adolf Tobena Alberto Fernandez-Teruel Google Regina Lopez-Aumatell Elia Vicens-Costa Esther Martinez-Membrives Toni Canete Gloria Blazquez Adolf Tobena Alberto Fernandez-Teruel Google Scholar Regina Lopez-Aumatell Elia Vicens-Costa Esther Martinez-Membrives Toni Canete Gloria Blazquez Adolf Tobena Alberto Fernandez-Teruel PubMed Regina Lopez-Aumatell Elia Vicens-Costa Esther Martinez-Membrives Toni Canete Gloria Blazquez Adolf Tobena Alberto Fernandez-Teruel Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Spatial learning in the genetically heterogeneous N/Nih-HS rat stock: relationship with anxiety levels in comparison with the Roman rat strains

Event Abstract Back to Event Spatial learning in the genetically heterogeneous N/Nih-HS rat stock: relationship with anxiety levels in comparison with the Roman rat strains Esther Martinez-Membrives1*, Elia Vicens-Costa1, Regina Lopez-Aumatell1, Toni Canete1, Gloria Blazquez1, Adolf Tobena1 and Alberto Fernandez-Teruel1 1 Universidad Autonoma de Barcelona, Unidad de Psicologia Medica, Dep. Psiquiatría y Medicina Legal, Instituto de Neurociencias, Facultad de Medicina, Spain The genetically heterogeneous (N/Nih-HS) rat stock constitutes an unique resource for the identification and fine mapping of genetic locus influencing complex and quantitative traits (QTL). No study has been done thus far with these N/Nih-HS genetically heterogeneous rats regarding their learning abilities. Thus, the present study constitutes a first approach to the spatial learning and memory profiles of those rats. We have compared the N/Nih-HS rat stock with the RLA-I and RHA-I rat strains as concerns to their levels of anxiety as well as in a shortened procedure of the Morris Water Maze task which has shown to be valid for measuring spatial learning and memory. The results show that, 1) the N/Nih-HS rat stock displays a rather good ability for spatial learning (i.e. their performance is comparable or even better than that of the “good learner” RLA-I rats); 2) pigmented N/Nih-HS rats show better learning ability than their albino counterparts, and 3) N/Nih-HS rats with relatively higher levels of anxiety display better spatial learning ability than low anxious rats. The results are discussed in the context of the controversial relationships between anxiety and learning efficiency. Acknowledgements" Supported by EURATools (European Commission Contract no. LSHG-CT-2005-019015). Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Martinez-Membrives E, Vicens-Costa E, Lopez-Aumatell R, Canete T, Blazquez G, Tobena A and Fernandez-Teruel A (2009). Spatial learning in the genetically heterogeneous N/Nih-HS rat stock: relationship with anxiety levels in comparison with the Roman rat strains. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.226 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Jun 2009; Published Online: 11 Jun 2009. * Correspondence: Esther Martinez-Membrives, Universidad Autonoma de Barcelona, Unidad de Psicologia Medica, Dep. Psiquiatría y Medicina Legal, Instituto de Neurociencias, Facultad de Medicina, Barcelona, Spain, Esther.Martinez@uab.es Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Esther Martinez-Membrives Elia Vicens-Costa Regina Lopez-Aumatell Toni Canete Gloria Blazquez Adolf Tobena Alberto Fernandez-Teruel Google Esther Martinez-Membrives Elia Vicens-Costa Regina Lopez-Aumatell Toni Canete Gloria Blazquez Adolf Tobena Alberto Fernandez-Teruel Google Scholar Esther Martinez-Membrives Elia Vicens-Costa Regina Lopez-Aumatell Toni Canete Gloria Blazquez Adolf Tobena Alberto Fernandez-Teruel PubMed Esther Martinez-Membrives Elia Vicens-Costa Regina Lopez-Aumatell Toni Canete Gloria Blazquez Adolf Tobena Alberto Fernandez-Teruel Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Context conditioned fear and anxiety in the acquisition of two-way active avoidance in the genetically heterogeneous N/Nih rat stock: comparison with the Roman rat strains

Context conditioned fear and anxiety in the acquisition of two-way active avoidance in the genetically heterogeneous N/Nih rat stock: comparison with the Roman rat strains

Characterization of central and peripheral components of the hypothalamus–pituitary–adrenal axis in the inbred Roman rat strains

Several studies performed in outbred Roman high- and low-avoidance lines (RHA and RLA, respectively) have demonstrated that the more anxious line (RLA) is characterized by a higher hypothalamic-pituitary-adrenal (HPA) response to certain stressors than the less anxious one (RHA). However, inconsistent results have also been reported. Taking advantage of the generation of an inbred colony of RLA and RHA rats (RHA-I and RLA-I, respectively), we have characterized in the two strains not only resting and stress levels of peripheral HPA hormones but also central components of the HPA axis, including CRF gene expression in extra-hypothalamic areas. Whereas resting levels of ACTH and corticosterone did not differ between the strains, a greater response to a novel environment was found in RLA-I as compared to RHA-I rats. RLA-I rats showed enhanced CRF gene expression in the paraventricular nucleus (PVN) of the hypothalamus, with normal arginin-vasopressin gene expression in both parvocellular and magnocellular regions of the PVN. This enhanced CRF gene expression is not apparently related to altered negative corticosteroid feedback as similar levels of expression of brain glucorticoid and mineralocorticoid receptors were found in the two rat strains. CRF gene expression tended to be higher in the central amygdala and it was significantly higher in the dorsal region of the bed nucleus of stria terminalis (BNST) of RLA-I rats, while no differences appeared in the ventral region of BNST. Considering the involvement of CRF and the BNST in anxiety and stress-related behavioral alterations, the present data suggest that the CRF system may be a critical neurobiological substrate underlying differences between the two rat strains.

Regional adaptations in PSD-95, NGFI-A and secretogranin gene transcripts related to vulnerability to behavioral sensitization to amphetamine in the Roman rat strains

Genetically selected for high or low two-way active avoidance, Roman high-avoidance (RHA) and Roman low-avoidance (RLA) rats differ in their central dopaminergic activity, sensation/novelty- and substance-seeking profiles. These animals are, therefore, well suited to identify anatomical and neurochemical concomitants of behavioral sensitization, a phenomenon linked to addictive liability. We submitted inbred RHA (RHA-I), inbred RLA (RLA-I) and Sprague–Dawley-OFA (SD-OFA) rats to a sensitization regimen with amphetamine and studied the behavioral response to an amphetamine challenge after a 2-week withdrawal period. The expression patterns of nerve growth factor inducible clone A (NGFI-A), secretogranin, post-synaptic density protein of 95 Kd (PSD-95), prodynorphin and proenkephalin mRNA were also analyzed using in situ hybridization, after the challenge with amphetamine. RHA-I rats showed stronger sensitization than SD-OFA rats. RLA-I rats did not show sensitization but were hyper-reactive to amphetamine. Expression of behavioral sensitization in RHA-I rats activated secretogranin and PSD-95 mRNA in the nucleus accumbens core. On the other hand, high induction of NGFI-A mRNA in the central amygdala was observed in RLA-I rats when they experienced amphetamine for the first time in the challenge. Our results reveal that 1) the acute locomotor response to amphetamine does not predict vulnerability to behavioral sensitization and 2) differences in vulnerability to sensitization may involve distinctive cellular adaptations at particular brain locations which may be related to addictive vulnerability.

Divergent anatomical pattern of D 1 and D 3 binding and dopamine- and cyclic AMP-regulated phosphoprotein of 32 kDa mRNA expression in the Roman rat strains: Implications for drug addiction

Autoradiography analysis of D 1, D 2 and D 3 dopamine receptors and in situ hybridization analysis of mRNA for dopamine and cAMP regulated phosphoprotein of 32 kDa (DARPP-32) were performed in brains of naïve Roman high avoidance (RHA) and Roman low avoidance (RLA) inbred rats. These strains, genetically selected for high (RHA) or extremely low (RLA) active avoidance acquisition in the two-way shuttle box, differ in indices of dopaminergic activity along with sensation/novelty and substance-seeking behavioral profiles. The present study shows no differences in D 2 receptor binding between the two strains. In contrast, the D 1 and D 3 receptor binding in the nucleus accumbens was higher in RHA-I rats, whereas RLA-I rats show higher D 3 binding in the Calleja islands. Together with previous evidence showing behavioral and presynaptic differences related to the dopamine system, the present results suggest a higher dopaminergic tone at the nucleus accumbens shell in RHA-I rats. Besides, the comparison of the expression pattern of DARPP-32 mRNA with that of dopamine receptor binding revealed a mismatch in some amygdala nuclei. In some cortical structures (prelimbic and cingulate cortices, the dentate gyrus) as well as in the central amygdala, RHA-I rats showed higher DARPP-32 mRNA expression than RLA-I rats. Hence, RHA-I and RLA-I rats may be a useful tool to identify dopamine-related mechanisms that predispose to drug and alcohol dependence.

Reduced ethanol response in the alcohol‐preferring RHA rats and neuropeptide mRNAs in relevant structures

Roman rat strains, genetically selected for high (RHA) or low (RLA) active avoidance acquisition in the two-way shuttle box, differ in dopaminergic activity. These two strains appear to be a valid laboratory model of divergent sensation/novelty and substance-seeking profiles. RHA rats show higher ethanol intake and preference than do RLA rats, and it was suggested that RHA rats are more tolerant than RLA to the effects of alcohol. In the hole-board test, we found that the non-alcohol-preferring RLA rats showed enhanced responsiveness to the stimulatory effects of intraperitoneal administration of 0.25 g/kg ethanol when compared with RHA rats. In situ hybridization analysis showed higher levels of preprodynorphin in the accumbens shell and higher levels of preproenkephalin in the cingulate cortex in RHA rats. RLA rats showed higher levels of enkephalin gene transcripts in restricted areas of the dorsal striatum. Finally, differences in cholecystokinin gene transcript, suggestive of a different arrangement of certain interneurons, were found in different cortical areas. The differences in peptide gene expression found between the two strains might reflect the differences in alcohol preference and sensitivity. RHA rats may have more predictive value than other rodent alcoholism models, as high initial tolerance to ethanol is a risk factor for alcoholism in humans.