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Differences in the performance of NK1R-/- ('knockout') and wildtype mice in the 5‑Choice Continuous Performance Test
Ashley J Porter1, Katharine Pillidge1, S Clare Stanford1
1Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Abstract:
Mice lacking functional NK1 (substance P-preferring) receptors typically display excessive inattentiveness (omission errors) and impulsivity (premature responses) when compared with wildtypes in the 5-Choice Serial Reaction-Time Test (5-CSRTT). These abnormal behaviours are analogous to those seen in humans suffering from Attention Deficit Hyperactivity Disorder (ADHD). Here we used the 5-Choice Continuous‑Performance Test (5C-CPT) to ascertain whether NK1R-/- mice also display excessive false alarms (an inappropriate response to a 'no-go' signal), which is another form of impulsive behaviour. NK1R-/- mice completed more trials than wildtypes, confirming their ability to learn and carry out the task. At the start of Stage 1 of training, but not subsequently, they also scored more premature responses than wildtypes. When the mice were tested for the first time, neither false alarms nor premature responses was higher in NK1R-/- mice than wildtypes but, as in the 5-CSRTT, the latter behaviour was strongly dependent on time of day. NK1R-/- mice expressed excessive perseveration during all stages of the 5C-CPT. This behaviour is thought to reflect compulsive checking, which is common in ADHD patients. These findings point to differences in the 5-CSRTT and 5C-CPT protocols that could be important for distinguishing why the cognitive performance and response control of NK1R-/- mice differs from their wildtypes. The results further lead to the prediction that ADHD patients with polymorphism of the TACR1 gene (the human equivalent of Nk1r) would express more perseveration, but not false alarms, in Continuous Performance Tests when compared with other groups of subjects.
Insights
Mice lacking NK1 receptors show perseveration, a behavior linked to ADHD. This study used the 5-Choice Continuous Performance Test to explore cognitive differences in these mice compared to wildtypes.
Area of Science:
- Neuroscience
- Behavioral Science
- Pharmacology
Background:
- Mice lacking functional NK1 (substance P-preferring) receptors exhibit inattentiveness and impulsivity, mirroring Attention Deficit Hyperactivity Disorder (ADHD) symptoms.
- Previous studies using the 5-Choice Serial Reaction-Time Test (5-CSRTT) highlighted these behavioral deficits.
Purpose of the Study:
- To investigate whether NK1 receptor knockout (NK1R-/-) mice display excessive false alarms in the 5-Choice Continuous Performance Test (5C-CPT).
- To further characterize the cognitive performance and response control differences between NK1R-/- mice and wildtypes using the 5C-CPT.
Main Methods:
- Utilized the 5-Choice Continuous Performance Test (5C-CPT) to assess cognitive functions in NK1R-/- mice and wildtype controls.
- Monitored omission errors, premature responses, false alarms, and perseveration across different training stages.
Main Results:
- NK1R-/- mice completed more trials, indicating task learning ability.
- Excessive perseveration was observed in NK1R-/- mice throughout the 5C-CPT, a behavior associated with compulsive checking in ADHD.
- Premature responses were elevated at the start of training but not consistently, and false alarms were not significantly higher in NK1R-/- mice.
Conclusions:
- The 5C-CPT reveals distinct cognitive deficits in NK1R-/- mice, particularly perseveration, which differs from findings in the 5-CSRTT.
- Differences in test protocols may explain variations in observed cognitive performance and response control.
- Suggests that individuals with TACR1 gene polymorphisms (linked to NK1 receptors) may exhibit increased perseveration in Continuous Performance Tests, relevant to ADHD research.
