Yan, TC; Dudley, JA; Weir, RK; Grabowska, EM; Pena-Oliver, Y; Ripley, TL; Hunt, SP; ... Stanford, C; + view all Yan, TC; Dudley, JA; Weir, RK; Grabowska, EM; Pena-Oliver, Y; Ripley, TL; Hunt, SP; Stephens, DN; Stanford, C; - view fewer (2011) Performance Deficits of NK1 Receptor Knockout Mice in the 5-Choice Serial Reaction-Time Task: Effects of d-Amphetamine, Stress and Time of Day. PLOS ONE , 6 (3) , Article e17586. 10.1371/journal.pone.0017586.

Preview	PDF 1301692.pdf Available under License : See the attached licence file. Download (764kB)
	PDF (licence) RPS deposit licence.pdf Access restricted to UNSPECIFIED Available under License : See the attached licence file. Download (94kB)
	PDF (licence) RPS deposit licence.pdf Access restricted to UNSPECIFIED Download (94kB)

Abstract

Background: The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon.Methods and Results: The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning.Conclusion: In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies.

Available Versions of this Item

• Performance Deficits of NK1 Receptor Knockout Mice in the 5-Choice Serial Reaction-Time Task: Effects of d-Amphetamine, Stress and Time of Day. (deposited 30 Mar 2011 21:42)
  • Performance Deficits of NK1 Receptor Knockout Mice in the 5-Choice Serial Reaction-Time Task: Effects of d-Amphetamine, Stress and Time of Day. (deposited 20 May 2013 09:07) [Currently Displayed]

Download activity - last month

Export as JSONXMLCSV

Download activity - last 12 months

Export as JSONCSVXML

Downloads by country - last 12 months

Export as XMLCSVJSON

Archive Staff Only

View Item