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

Porter, Alfred W.; Pillidge, Katharine; Stanford, S Clare; Young, Jared W.

doi:10.1016/j.bbr.2015.10.045

Cited by 14 publications

(26 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bars show mean±standard error of the mean (SEM) score for the five test conditions. White bars: wild types; shaded bars: NK1R-/- mice; NI-2: no-injection (results for NI-1 are reported in Porter et al, 2016); VEH: vehicle; MPH3, MPH10 and MPH30: methylphenidate 3, 10 and 30 mg/kg, respectively. Lines linking pairs of data indicate a statistically significant difference between the two genotypes at p <0.05 at least.…”

Section: Resultsmentioning

confidence: 99%

“…The protocol for training mice in the 5C-CPT is explained fully elsewhere (Porter et al, 2016; Young et al, 2009), but essential elements of the procedure are reported below.…”

Section: Methodsmentioning

confidence: 99%

“…Each animal was trained/tested at the same time each day. The criteria for graduation through each of the four stages of training are explained in full in Young et al (2009) with modifications specified in Porter et al (2016).…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we compared the behaviour of NK1R–/- mice and their wild types in the 5-Choice Continuous Performance Test (5C-CPT; Porter et al, 2016). This procedure is regarded as an analogue of those used to study human cognitive performance because it incorporates both ‘no-go’ (non-target) and ‘go’ (target) light signals, unlike the 5CSRTT, which uses only the latter signal/response contingency.…”

Section: Introductionmentioning

confidence: 99%

“…Because NK1R-/- mice completed more trials (‘total trials’) than wild types in our previous study using this procedure (Porter et al, 2016), we also compared the effects of methylphenidate on this measure of ‘productivity’ in the two genotypes.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Perseveration by NK1R-/- (‘knockout’) mice is blunted by doses of methylphenidate that affect neither other aspects of their cognitive performance nor the behaviour of wild-type mice in the 5-Choice Continuous Performance Test

et al. 2016

Self Cite

View full text Add to dashboard Cite

The underlying cause(s) of abnormalities expressed by patients with attention deficit hyperactivity disorder (ADHD) have yet to be delineated. One factor that has been associated with increased vulnerability to ADHD is polymorphism(s) of TACR1, which is the human equivalent of the rodent NK1 (substance P-preferring) receptor gene (Nk1r). We have reported previously that genetically altered mice, lacking functional NK1R (NK1R–/–), express locomotor hyperactivity, which was blunted by the first-line treatment for ADHD, methylphenidate. Here, we compared the effects of this psychostimulant (3, 10 and 30 mg/kg, intraperitoneally) on the behaviour of NK1R-/- mice and their wild types in the 5-Choice Continuous Performance Test, which emulates procedures used to study attention and response control in ADHD patients. Methylphenidate increased total trials (a measure of ‘productivity’) completed by wild types, but not by NK1R-/- mice. Conversely, this drug reduced perseveration by NK1R-/- mice, but not by wild types. Other drug-induced changes in key behaviours were not genotype dependent, especially at the highest dose: for example, % omissions (an index of inattentiveness) was increased, whereas % false alarms and % premature responses (measures of impulsivity) declined in both genotypes, indicating reduced overall response. These findings are discussed in the context of the efficacy of methylphenidate in the treatment of ADHD. Moreover, they lead to several testable proposals. First, methylphenidate does not improve attention in a subgroup of ADHD patients with a functional deficit of TACR1. Second, these patients do not express excessive false alarms when compared with other groups of subjects, but they do express excessive perseveration, which would be ameliorated by methylphenidate.

show abstract

Section: Resultsmentioning

confidence: 99%

“…The protocol for training mice in the 5C-CPT is explained fully elsewhere (Porter et al, 2016; Young et al, 2009), but essential elements of the procedure are reported below.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Perseveration by NK1R-/- (‘knockout’) mice is blunted by doses of methylphenidate that affect neither other aspects of their cognitive performance nor the behaviour of wild-type mice in the 5-Choice Continuous Performance Test

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

The Five‐Choice Continuous Performance Task (5C‐CPT): A Cross‐Species Relevant Paradigm for Assessment of Vigilance and Response Inhibition in Rodents

Cope

Young

2017

CP Neuroscience

Self Cite

View full text Add to dashboard Cite

Deficits in the domains of attention and response inhibition are central to many psychiatric disorders. As such, animal models of disorders purporting to replicate these behavioral deficits first require tests that can accurately assess the behaviors with high fidelity. The gold-standard clinical test of attention and response inhibition is the continuous performance test (CPT). Although there are a number of CPTs, all share the premise of responding to target stimuli and inhibiting from responding to non-target stimuli. The recently developed rodent five-choice CPT (5C-CPT) requires similar behavioral responses, enabling signal detection parameter calculations. With demonstrable feasibility for rodent testing, the 5C-CPT permits/facilitates: (1) delineation of neural mechanisms underlying these behaviors; (2) multifactorial analyses of the complex interplay between genetic and environmental manipulations relevant to psychiatric disorders; and hence (3) development of novel targeted treatments. All data to date indicate that the rodent 5C-CPT described here has direct translatability to clinical CPTs, producing equivalent measures of behavior in experimental animals to those assessed in humans. The 5C-CPT task provides an important tool toward delineating these mechanisms and developing treatments. However, it is also complex, with long training times and nuances requiring a thorough understanding before utilization. This unit will enable researchers to avoid potential missteps, greatly increasing the likelihood of success. © 2017 by John Wiley & Sons, Inc.

show abstract

Visual discrimination and inhibitory control deficits in mouse models of Down syndrome: A pilot study using rodent touchscreen technology

Siegel

Bianchi

Guedj

2023

J of Neuroscience Research

View full text Add to dashboard Cite

Several non‐verbal cognitive and behavioral tests have been developed to assess learning deficits in humans with Down syndrome (DS). Here we used rodent touchscreen paradigms in adult male mice to investigate visual discrimination (VD) learning and inhibitory control in the Dp(16)1/Yey (C57BL/6J genetic background), Ts65Dn (mixed B6 X C3H genetic background) and Ts1Cje (C57BL/6J genetic background) mouse models of DS. Dp(16)1/Yey and Ts1Cje models did not exhibit motivation or learning deficits during early pre‐training, however, Ts1Cje mice showed a significant learning delay after the introduction of the incorrect stimulus (late pre‐training), suggesting prefrontal cortex defects in this model. Dp(16)1/Yey and Ts1Cje mice display learning deficits in VD but these deficits were more pronounced in the Dp(16)1/Yey model. Both models also exhibited compulsive behavior and abnormal cortical inhibitory control during Extinction compared to WT littermates. Finally, Ts65Dn mice outperformed WT littermates in pre‐training stages by initiating a significantly higher number of trials due to their hyperactive behavior. Both Ts65Dn and WT littermates showed poor performance during late pre‐training and were not tested in VD. These studies demonstrate significant learning deficits and compulsive behavior in the Ts1Cje and Dp(16)1/Yey mouse models of DS. They also demonstrate that the mouse genetic background (C57BL/6J vs. mixed B6 X C3H) and the absence of hyperactive behavior are key determinants of successful learning in touchscreen behavioral testing. These data will be used to select the mouse model that best mimics cognitive deficits in humans with DS and evaluate the effects of future therapeutic interventions.

show abstract

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

Cited by 14 publications

References 73 publications

Perseveration by NK1R-/- (‘knockout’) mice is blunted by doses of methylphenidate that affect neither other aspects of their cognitive performance nor the behaviour of wild-type mice in the 5-Choice Continuous Performance Test

Perseveration by NK1R-/- (‘knockout’) mice is blunted by doses of methylphenidate that affect neither other aspects of their cognitive performance nor the behaviour of wild-type mice in the 5-Choice Continuous Performance Test

The Five‐Choice Continuous Performance Task (5C‐CPT): A Cross‐Species Relevant Paradigm for Assessment of Vigilance and Response Inhibition in Rodents

Visual discrimination and inhibitory control deficits in mouse models of Down syndrome: A pilot study using rodent touchscreen technology

Contact Info

Product

Resources

About