Validation of behavioral phenotypes in the BACHD rat model.

Huntington disease (HD) is a neurodegenerative disorder caused by a polyglutamine expansion in the HTT gene. Various HD animal models have been generated to mimic the motor, cognitive and neuropsychiatric disturbances that affect HD patients. Reproducing disease phenotypes within these models is essential to identify reliable readouts for therapy studies.

BACHD rats expressing full-length mutant huntingtin exhibit differences in social behavior compared to wild-type littermates.

Background: Huntington disease (HD) is a devastating inherited neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms without any cure to slow down or stop the progress of the disease. The BACHD rat model for HD carrying the human full-length mutant huntingtin protein (mHTT) with 97 polyQ repeats has been recently established as a promising model which reproduces several HD-like features. While motor and cognitive functions have been characterized in BACHD rats, little is known about their social phenotype.

Hippocampal extracellular matrix alterations contribute to cognitive impairment associated with a chronic depressive-like state in rats.

Patients with depression often suffer from cognitive impairments that contribute to disease burden. We used social defeat-induced persistent stress (SDPS) to induce a depressive-like state in rats and then studied long-lasting memory deficits in the absence of acute stressors in these animals. The SDPS rat model showed reduced short-term object location memory and maintenance of long-term potentiation (LTP) in CA1 pyramidal neurons of the dorsal hippocampus.

The BACHD Rat Model of Huntington Disease Shows Specific Deficits in a Test Battery of Motor Function.

: Huntington disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive and neuropsychiatric symptoms. HD is usually diagnosed by the appearance of motor deficits, resulting in skilled hand use disruption, gait abnormality, muscle wasting and choreatic movements. The BACHD transgenic rat model for HD represents a well-established transgenic rodent model of HD, offering the prospect of an in-depth characterization of the motor phenotype.

Home-cage anxiety levels in a transgenic rat model for Spinocerebellar ataxia type 17 measured by an approach-avoidance task: The light spot test.

Background: Measuring anxiety in a reliable manner is essential for behavioural phenotyping of rodent models such as the rat model for Spinocerebellar ataxia type 17 (SCA17) where anxiety is reported in patients. An automated tool for assessing anxiety within the home cage can minimize human intervention, stress of handling, transportation and novelty.

New Method: We applied the anxiety test "light spot" (LS) (white led directed at the food-hopper) to our transgenic SCA17 rat model in the PhenoTyper 4500 to extend the knowledge of this automated tool for behavioural phenotyping and to verify an anxiety-like phenotype at three different disease stages for use in future therapeutic studies.

Short- and long-term behavioral analysis of social interaction, ultrasonic vocalizations and social motivation in a chronic phencyclidine model.

Phencyclidine (PCP) has been suggested to induce symptoms of schizophrenia. However, animal models using PCP administration have produced ambiguous results thus far. It seems that acute effects are similar to symptoms of schizophrenia, however, it is not clear if PCP can induce permanent behavioral changes that reflect schizophrenic-like symptoms.

Anxiety and risk assessment-related traits in a rat model of Spinocerebellar ataxia type 17.

Anxiety as a common feature of several neurodegenerative/polyglutamine diseases is an important aspect for the face validity of an animal model for Spinocerebellar Ataxia type 17 (SCA17). Risk assessment and anxiety-like traits were characterised in 3-6-9 months old rats of a transgenic model for SCA17 using the standard behavioural test elevated plus maze. In addition, c-Fos immunostainings in the basolateral amygdala evaluated neuronal activation in correlation to the behavioural responses.

Novel approach to automatically classify rat social behavior using a video tracking system.

Background: In the past, studies in behavioral neuroscience and drug development have relied on simple and quick readout parameters of animal behavior to assess treatment efficacy or to understand underlying brain mechanisms. The predominant use of classical behavioral tests has been repeatedly criticized during the last decades because of their poor reproducibility, poor translational value and the limited explanatory power in functional terms.

New Method: We present a new method to monitor social behavior of rats using automated video tracking.

Automated quantitative analysis to assess motor function in different rat models of impaired coordination and ataxia.

Background: An objective and automated method for assessing alterations in gait and motor coordination in different animal models is important for proper gait analysis. The CatWalk system has been used in pain research, ischemia, arthritis, spinal cord injury and some animal models for neurodegenerative diseases.

New Method: Our goals were to obtain a comprehensive gait analysis of three different rat models and to identify which motor coordination parameters are affected and are the most suitable and sensitive to describe and detect ataxia with a secondary focus on possible training effects.

Reproducibility and relevance of future behavioral sciences should benefit from a cross fertilization of past recommendations and today's technology: "Back to the future".

Thanks to the discovery of novel technologies and sophisticated analysis tools we can now 'see' molecules, genes and even patterns of gene expression, which have resulted in major advances in many areas of biology. Recently, similar technologies have been developed for behavioral studies. However, the wide implementation of such technological progress in behavioral research remains behind, as if there are inhibiting factors for accepting and adopting available innovations.

A sustained depressive state promotes a guanfacine reversible susceptibility to alcohol seeking in rats.

High rates of comorbidity between alcohol use disorder (AUD) and major depressive disorder (MDD) are reported. Preclinical models examining effects of primary depression on secondary AUD are currently absent, preventing adequate testing of drug treatment. Here, we combined social defeat-induced persistent stress (SDPS) and operant alcohol self-administration (SA) paradigms to assess causality between these two neuropsychiatric disorders.

An automated system for the recognition of various specific rat behaviours.

The automated measurement of rodent behaviour is crucial to advance research in neuroscience and pharmacology. Rats and mice are used as models for human diseases; their behaviour is studied to discover and develop new drugs for psychiatric and neurological disorders and to establish the effect of genetic variation on behavioural changes. Such behaviour is primarily labelled by humans.

Announced reward counteracts the effects of chronic social stress on anticipatory behavior and hippocampal synaptic plasticity in rats.

Chronic stress causes insensitivity to rewards (anhedonia) in rats, reflected by the absence of anticipatory behavior for a sucrose-reward, which can be reversed by antidepressant treatment or repeated announced transfer to an enriched cage. It was, however, not clear whether the highly rewarding properties of the enriched cage alone caused this reversal or whether the anticipation of this reward as such had an additional effect. Therefore, the present study compared the consequences of the announcement of a reward to the mere effect of a reward alone with respect to their efficacy to counteract the consequences of chronic stress.

Announced rewards counteract the impairment of anticipatory behaviour in socially stressed rats.

It is known that stress can influence the sensitivity to rewarding stimuli. Previous observations revealed that socially stressed rats do not display an appetitive behavioural response in anticipation of a reward. A previous study showed that this insensitivity to rewards (anhedonia) could be restored by chronic administration of an antidepressant.

Standard housed rats are more sensitive to rewards than enriched housed rats as reflected by their anticipatory behaviour.

The present study was designed to investigate the effects of potentially stressful standard housing conditions for laboratory rats on the sensitivity to rewards as reflected by their anticipatory behaviour for sucrose. This anticipatory response is evoked in a conditioning paradigm in which a sucrose reward is repeatedly announced by a stimulus. The underlying neurocircuitry of this anticipatory response in expectation of a reward involves mesolimbic dopaminergic systems of which it is known that they can be sensitised by stressors.

Anticipation is differently expressed in rats (Rattus norvegicus) and domestic cats (Felis silvestris catus) in the same Pavlovian conditioning paradigm.

In rats (Rattus norvegicus) anticipation to an oncoming food reward in an appetitive Pavlovian conditioning procedure is expressed as an increase of behavioural transitions, i.e. hyperactivity.