Assessment of attention in male and female Brattleboro rats using a self-paced five-choice serial reaction time task

Berquist, Michael D.; Mooney‐Leber, Sean M.; Feifel, David; Prus, Adam J.

doi:10.1016/j.brainres.2013.09.012

Cited by 10 publications

(9 citation statements)

References 33 publications

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“…Other studies, comparing BRAT and LE rats, have also reported cognitive deficits, such as impaired fear conditioning, impaired acquisition and maintenance of passive avoidance behavior and deficits in spatial learning in a delayed alternation task [38]. Moreover, Feifel et al [35] showed that BRAT rats presented a natural deficit in social discrimination, as they spent a comparable amount of time exploring a novel and a familiar rat.…”

Section: ) Brattleboro Ratsmentioning

confidence: 97%

“…BRAT rats display an innate deficit of PPI [34]- [39]. Berquist et al [38] hypothesized that such deficit may compromise performance, in tasks assessing attention, by diminishing the ability to shift attention between stimuli. Interestingly, of relevance for the predictive validity of the BRAT rat strain is the fact that a wide range of antipsychotics, such as haloperidol, clozapine and risperidone (olanzapine had a less robust effect), reversed the deficits in PPI.…”

Section: ) Brattleboro Ratsmentioning

confidence: 99%

“…The authors interpreted that such an impaired social discrimination is due to a deficit in social memory rather than a nonspecific reduction in general activity or in social motivation, because saline-treated BRAT rats and LE rats spent almost the same time interacting with a juvenile rat during the acquisition phase. Berquist et al [38] reported recently that male BRAT rats employed more time (16.8% longer) than LE rats to complete a task based on the 5-choice serial reaction time (5-CSRT) task, while there were no between-strain differences in females.…”

Section: ) Brattleboro Ratsmentioning

confidence: 99%

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Genetic Rat Models of Schizophrenia-Relevant Symptoms

Río¹,

Oliveras²,

Cañete³

et al. 2014

WJNS

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It is recognized that developing valid animal models is essential for the research on the neurobiological mechanisms of (and treatments for) psychiatric disorders, even when these are as complex as schizophrenia. To be considered a valid analogue of the disorder, a given model should present good face validity (i.e. similarity of symptoms), good predictive validity (i.e. similarity of treatment effects and potential for discovering novel treatments) and enough construct validity (i.e. the model should help discover neurobiological mechanisms underlying the disorder or some relevant symptoms). The complexity of symptoms (positive, negative and cognitive) of schizophrenia makes it a very difficult task for a model to mimic all the main features of the disorder, but some rodent (mouse and rat) models have behavioural and even neurobiological phenotype characteristics resembling positive-like symptoms, cognitive symptoms and some neurochemical features of schizophrenia. As several recent works have already reviewed the main behavioural and developmental models, as well as the most used drug-induced, lesion-induced and genetic mouse models, the present review focuses on describing the most relevant genetically-based rat models of schizophrenia-relevant symptoms. Thus, we discuss several selective breeding programs leading to rat lines/strains which present impaired prepulse inhibition (PPI) of the acoustic startle response and (in some cases) latent inhibition deficits (both of which may be considered as endophenotypes of schizophrenia related with pre-attentive processes and attention, respectively), as well as other schizophrenia-relevant symptoms (e.g. learning deficits). Evidence is presented for the effects of genetic background on PPI (and other symptoms/phenotypes), as well as for environmental influences on genetic predisposition to enhanced apomorphine (mixed dopamine receptor agonist) effects. Some of the described rat models appear to present face validity and, to a certain extent, construct validity. While efforts should be made to evaluate the predictive validity of these genetic rat models, we propose that they have the advantage (over mouse knockouts, for example) of better representing "normal" genetic, neurobiological and phenotype variation, * Corresponding author.C. del Río et al. 262thus allowing the study of associations among them by means of genetic mapping or gene expression studies.

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Section: ) Brattleboro Ratsmentioning

confidence: 97%

Section: ) Brattleboro Ratsmentioning

confidence: 99%

Section: ) Brattleboro Ratsmentioning

confidence: 99%

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Genetic Rat Models of Schizophrenia-Relevant Symptoms

Río¹,

Oliveras²,

Cañete³

et al. 2014

WJNS

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“…Nevertheless, the AVP-deficient Brattleboro rat shows SCZrelated symptoms, which develop spontaneously. This strain, in addition to exhibiting a diabetes insipidus-like phenotype characterized by polydipsia and polyuria, have been shown to have a number of cognitive and behavioral abnormalities that are analogous to those seen in SCZ patients, including abnormalities in memory, emotional reactivity, social recognition, motivation and attention [39][40][41][42][43][44]. As AVP is not clearly connected to disease etiology, epigenetic contribution is more likely leading to secondary changes in different neurotransmitter systems [45,46].…”

Section: Introductionmentioning

confidence: 99%

Possible contribution of epigenetic changes in the development of schizophrenia-like behavior in vasopressin-deficient Brattleboro rats

Demeter

Török

Fodor

et al. 2016

Behavioural Brain Research

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Schizophrenia-like symptoms were detected in vasopressin-deficient (di/di) Brattleboro rats, and it was also suggested that schizophrenia might have an epigenetic component. We aimed to clarify if epigenetic changes contribute to schizophrenia-like behavior of this strain. Behavioral (locomotion by telemetry, cognition by novel object recognition, social recognition and social avoidance test, attention by pre-pulse inhibition) and epigenetic differences were compared between wild type and di/di animals. DNA methyltransferase1 (DNMT1), DNMT3a, as well as COMT, GAD, VGLUT1, 5HT2A, BDNF mRNA levels in prefrontal brain region and hippocampus were studied by qRT-PCR. Histone3 (H3) and H4 acetylation (Ac) were studied by western-blot followed by region specific examination of H3 lysine9 (K9) acetylation by immunohistochemistry. Impaired cognitive, social and attention behavior of di/di rats confirmed schizophrenia-like symptoms in our local colony. The pan-AcH3 immunoreactivity was lower in prefrontal region and elevated in the hippocampus of di/di animals. We found lower immunopositive cell number in the dorsal peduncular prefrontal cortex and the ventral lateral septum and increased AcH3K9 immunoreactivity in CA1 region of di/di animals. There were no major significant alterations in the studied mRNA levels. We confirmed that Brattleboro rat is a good preclinical model of schizophrenia. Its schizophrenia-like behavioral alteration was accompanied by changes in H3 acetylation in the prefrontal region and hippocampus. This may contribute to disturbances of many schizophrenia-related substances leading to development of schizophrenia-like symptoms. Our studies confirmed that not a single gene, rather fine changes in an array of molecules are responsible for the majority of schizophrenia cases.

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“…The final stimulus cue duration used for most studies varies from 0.5 to 2 sec, with a typical required minimum accuracy of 60% to 80% across all trials with training durations ranging from 60 to 120 days depending on the stringency of final training criteria. [2, 6] The typical outcome measures used to indicate levels of attention are %correct responses and %omissions (trials in which the subject fails to respond with a nose poke in any hole within a given time limit). However, both measures are dependent on the final cue duration used for the study.…”

Section: Introductionmentioning

confidence: 99%

Assessment of attention threshold in rats by titration of visual cue duration during the five choice serial reaction time task

Martin

Grigg

Kim

et al. 2015

Journal of Neuroscience Methods

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Background The 5 choice serial reaction time task (5CSRTT) is commonly used to assess attention in rodents. We sought to develop a variant of the 5CSRTT that would speed training to objective success criteria, and to test whether this variant could determine attention capability in each subject. New Method Fisher 344 rats were trained to perform a variant of the 5CSRTT in which the duration of visual cue presentation (cue duration) was titrated between trials based upon performance. The cue duration was decreased when the subject made a correct response, or increased with incorrect responses or omissions. Additionally, test day challenges were provided consisting of lengthening the intertrial interval and inclusion of a visual distracting stimulus. Results Rats readily titrated the cue duration to less than 1 sec in 25 training sessions or less (mean ± SEM, 22.9 ± 0.7), and the median cue duration (MCD) was calculated as a measure of attention threshold. Increasing the intertrial interval increased premature responses, decreased the number of trials completed, and increased the MCD. Decreasing the intertrial interval and time allotted for consuming the food reward demonstrated that a minimum of 3.5 sec is required for rats to consume two food pellets and successfully attend to the next trial. Visual distraction in the form of a 3 Hz flashing light increased the MCD and both premature and time out responses. Comparison with existing method The titration variant of the 5CSRTT is a useful method that dynamically measures attention threshold across a wide range of subject performance, and significantly decreases the time required for training. Task challenges produce similar effects in the titration method as reported for the classical procedure. Conclusions The titration 5CSRTT method is an efficient training procedure for assessing attention and can be utilized to assess the limit in performance ability across subjects and various schedule manipulations.

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Assessment of attention in male and female Brattleboro rats using a self-paced five-choice serial reaction time task

Cited by 10 publications

References 33 publications

Genetic Rat Models of Schizophrenia-Relevant Symptoms

Genetic Rat Models of Schizophrenia-Relevant Symptoms

Possible contribution of epigenetic changes in the development of schizophrenia-like behavior in vasopressin-deficient Brattleboro rats

Assessment of attention threshold in rats by titration of visual cue duration during the five choice serial reaction time task

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