Differences in the performance of NK1R−/− (‘knockout’) and wildtype mice in the 5‑Choice Continuous Performance Test

Highlights

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  We compared the behaviour of NK1R−/− mice and wildtypes in the 5-Choice Continuous Performance Test.

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  NK1R−/− mice did not express excess impulsivity (premature response or false alarms) in this test.

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  NK1R−/− mice expressed excessive perseveration, which is common in ADHD.

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  The findings point to a behavioural phenotype for ADHD patients with polymorphism of the TACR1 gene.

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.