Progressive Ratio Performance with Reset Option

AbstractReward and motivation deficits are prominent symptoms in many mood disorders, including depression. Similar reward and effort-related choice behavioral tasks can be used to study aspects of motivation in both rodents and humans. Chronic stress can precipitate mood disorders in humans and maladaptive reward and motivation behaviors in male rodents. However, while depression is more prevalent in women, there is relatively little known about whether chronic stress elicits maladaptive behaviors in female rodents in effort-related motivated tasks and whether there are any behavioral sex differences. Chronic nondiscriminatory social defeat stress (CNSDS) is a variation of chronic social defeat stress that is effective in both male and female mice. We hypothesized that CNSDS would reduce effort-related motivated and reward behaviors, including reducing sensitivity to a devalued outcome, reducing breakpoint in progressive ratio, and shifting effort-related choice behavior. Separate cohorts of adult male and female C57BL/6 J mice were divided into Control or CNSDS groups, exposed to the 10-day CNSDS paradigm, and then trained and tested in instrumental reward or effort-related behaviors. CNSDS reduced motivation to lever press in progressive ratio and shifted effort-related choice behavior from a high reward to a more easily attainable low reward in both sexes. CNSDS caused more nuanced impairments in outcome devaluation. Taken together, CNSDS induces maladaptive shifts in effort-related choice and reduces motivated lever pressing in both sexes.

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Coexistence of perseveration and apathy in the TDP-43Q331K knock-in mouse model of ALS–FTD

Translational Psychiatry ◽

10.1038/s41398-020-01078-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Eosu Kim ◽

Matthew A. White ◽

Benjamin U. Phillips ◽

Laura Lopez-Cruz ◽

Hyunjeong Kim ◽

...

Keyword(s):

Translational Research ◽

Cognitive Flexibility ◽

Visual Discrimination ◽

Response Rate ◽

Psychological Symptoms ◽

Progressive Ratio ◽

Maximal Response ◽

Behavioural Phenotype ◽

Rate Analysis ◽

Lateral Sclerosis

Abstract Perseveration and apathy are two of the most common behavioural and psychological symptoms of dementia (BPSDs) in amyotrophic lateral sclerosis–frontotemporal dementia (ALS–FTD). Availability of a validated and behaviourally characterised animal model is crucial for translational research into BPSD in the FTD context. We behaviourally evaluated the male TDP-43Q331K mouse, an ALS–FTD model with a human-equivalent mutation (TDP-43Q331K) knocked into the endogenous Tardbp gene. We utilised a panel of behavioural tasks delivered using the rodent touchscreen apparatus, including progressive ratio (PR), extinction and visual discrimination/reversal learning (VDR) assays to examine motivation, response inhibition and cognitive flexibility, respectively. Relative to WT littermates, TDP-43Q331K mice exhibited increased responding under a PR schedule. While elevated PR responding is typically an indication of increased motivation for reward, a trial-by-trial response rate analysis revealed that TDP-43Q331K mice exhibited decreased maximal response rate and slower response decay rate, suggestive of reduced motivation and a perseverative behavioural phenotype, respectively. In the extinction assay, TDP-43Q331K mice displayed increased omissions during the early phase of each session, consistent with a deficit in activational motivation. Finally, the VDR task revealed cognitive inflexibility, manifesting as stimulus-bound perseveration. Together, our data indicate that male TDP-43Q331K mice exhibit a perseverative phenotype with some evidence of apathy-like behaviour, similar to BPSDs observed in human ALS–FTD patients. The TDP-43Q331K knock-in mouse therefore has features that recommend it as a useful platform to facilitate translational research into behavioural symptoms in the context of ALS–FTD.

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Comparison of the reinforcing efficacy of two dopamine D2-like receptor agonists in rhesus monkeys using a progressive-ratio schedule of reinforcement

Pharmacology Biochemistry and Behavior ◽

10.1016/s0091-3057(02)00749-9 ◽

2002 ◽

Vol 72 (4) ◽

pp. 803-809 ◽

Cited By ~ 14

Author(s):

William L Woolverton ◽

Robert Ranaldi

Keyword(s):

Rhesus Monkeys ◽

Progressive Ratio ◽

Ratio Schedule ◽

Progressive Ratio Schedule ◽

Reinforcing Efficacy ◽

Schedule Of Reinforcement ◽

Receptor Agonists ◽

Dopamine D2

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Nucleus Accumbens Dopamine Depletions and Time-Constrained Progressive Ratio Performance

Pharmacology Biochemistry and Behavior ◽

10.1016/s0091-3057(99)00092-1 ◽

1999 ◽

Vol 64 (1) ◽

pp. 21-27 ◽

Cited By ~ 51

Author(s):

S Hamill ◽

J.T Trevitt ◽

K.L Nowend ◽

B.B Carlson ◽

J.D Salamone

Keyword(s):

Nucleus Accumbens ◽

Progressive Ratio

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