Symposium: Using behavioural approaches to measure apathy-like behaviour in rodents

Organiser: Lianne Robinson, University of Aberdeen, UK

Schedule: 15:30 – 17:10 Wednesday 15th May, Conference Suite 2A

15:30 – 15:50 Lianne Robinson – Development of a Behavioural Test Battery to assess Apathy-like Behaviours in Mouse Models of Neurodegeneration

Apathy is the most common behavioural and psychological symptom in Alzheimer’s Disease, Frontotemporal Dementia and Parkinson’s Disease. Modelling of apathy-like behaviour in animals has proven difficult with many studies focusing on specific symptoms of apathy. In this study a battery of different behavioural assays was successfully implemented to model some of the behavioural traits indicative of apathy-like symptoms  in transgenic mouse models of neurodegenerative diseases.

15:50 – 16:10 Nicole Edwards – The splash test as a model of rodent apathy

Major depressive disorder (MDD) has been identified as a risk factor for Alzheimer’s disease (AD), with evidence demonstrating that MDD exacerbates AD progression. Reduced activity, anhedonia and apathy, three core symptoms associated with MDD, were explored in the 5xFAD mouse model of amyloid pathology using the open field test, sucrose preference test and splash test, respectively.  Our data highlights that depression-like behaviour is independent of sex and genotype in 5xFAD mice.

16:10 – 16:30 Richard Brown – Measuring “apathy” in mouse models of AD

Apathy, a lack of motivation for goal-directed behaviour, is a symptom of Alzheimer’s disease. Mouse models of Alzheimer’s disease returned to the start box without entering the goal box or failed to eat the reward in the Hebb Williams Maze, showed reduced motivation to respond on tests of peak interval timing, and stopped responding in tests of reversal learning in the operant olfactometer, suggesting Apathy-like behaviour in these tests.

16:30 – 16:50 John Salamone – Modeling Aspects of Apathy in Rodents using Effort-based Choice Procedures.

Apathy is a complex symptom in humans, with multiple components including emotional flattening and reduced goal directed behavior. Effort-based choice tasks are used to assess the exertion of effort in goal-directed activity. Our laboratory has developed several behavioral tasks in rodents that assess the effects of pharmacological manipulations on effort-related choice. These studies are being used to model motivational symptoms in psychopathology such as anergia and apathy, which could have implications for psychiatric research.

16:50 – 17:10 Mercè Correa – The 3 choice-T-maze task with running wheel: a mice paradigm to evaluate preference for reinforcers that require vigor and the role of dopamine in anergia

Studies of behavioral activation are important for understanding some aspects of psychopathology. Symptoms such as anergia, apathy, and fatigue refer to a lack of behavioral activation seen in multiple psychiatric disorders. Our group has developed a T-maze task to assess spontaneous preferences between reinforcers that require vigorous activity versus sedentary ones. This rodent task could evaluate brain mechanisms implicated in decision-making processes involved in spontaneous preference for sustaining voluntarily vigorous behaviors over time.

Apathy is one of the earliest and most common behavioural and psychological symptoms in dementia and neurodegenerative diseases including Alzheimer’s disease (AD), frontotemporal dementia (FTD) and Parkinson’s disease (PD). It is also associated with other diseases including Huntington’s, major depressive disorder and negative symptoms of schizophrenia. In patients, apathy can include symptoms of loss of motivation, initiative, and interest, listlessness, and indifference, flattening of emotions, absence of drive and passion. Researchers have later refined this to a reduction in goal direct behaviours. Apathy assessment in human patients has centred on using clinical scales and questionnaires to assess symptoms including reduced social interactions and changes in activities and emotions. In addition, objective/measurable behavioural tests of reward-based decision-making tasks and assessments of executive function have also been utilised with studies revealing that apathy is related to executive dysfunction (disrupted abstract thinking, planning and performing of complex tasks). Unfortunately, the behavioural tests used to assess apathy in patients do not lend themselves to be directly translated to animals. Furthermore, considering the multi-dimensional aspects of apathy and the close link with depression/anhedonia there is a challenge to back translate apathy like behaviour observed in human patients to animal models.

Behavioural tests to assess apathy-like behaviour in animals have focussed on tests that measure reduced goal directed behaviour (effort-based tasks including progressive ratio reinforcement test) and reward-based activity, altered social interactions, reduced exploration/spontaneous activity similar to observations in clinical trials, or a decline in species-specific behaviours including nest building and burrowing. Such species-specific behaviours are seen as indicators of impaired motivation to perform daily life activities and are reminiscent of the reduced activities of daily living (ADLs) observed in patients with apathy.  

This symposium will bring together researchers working within the field of apathy to discuss how different behavioural methods can be utilised to assess apathy-like behaviour in rodent models, these translational approaches are necessary to advance our understanding of mechanisms underlying apathy and guide future therapeutic interventions.