title: Premature responses in the five-choice serial reaction time task reflect rodents' temporal strategies: evidence from no-light and pharmacological challenges.
abstract: The five-choice serial reaction time task (5-CSRTT) is regularly used to study attention and impulsivity. In the 5-CSRTT, rodents initiate a trial, then after an inter-trial interval (ITI), a light appears in one of five holes. Responding in the lit vs. unlit hole reflects attention (accuracy), while responding prematurely before a light appears is suggested to reflect impulsivity/response disinhibition. Comparison of rat and mouse 5-CSRTT performance has raised questions on the validity of premature responses as measuring impulsivity/response inhibition. To minimize effort, rodents may use a temporal strategy, enabling their "timing" of the ITI, minimizing the need to attend during this delay. Greater reliance on this strategy could result in premature responses due to "guesses" if their timing was poor/altered.
  
  
  
  To assess the degree to which rats and/or mice utilize a temporal strategy, we challenged performance using infrequent no-light trials during 5-CSRTT performance.
  
  
  
  Even when no light appeared when one was expected, rats responded ~60 % compared to ~40 % in mice, indicating a greater reliance on a temporal strategy by rats than by mice. Consistent with this hypothesis, rats made more premature responses than mice. Additional studies using a temporal discrimination task and a 5-CSRTT variant demonstrated that delta-9-tetrahydrocannabinol, the active ingredient in cannabis, slowed temporal perception and reduced premature responses.
  
  
  
  These data provide behavioral and pharmacological evidence indicating that premature responses are heavily influenced by temporal perception. Hence, they may reflect an aspect of waiting impulsivity, but not response disinhibition, an important distinction for translational clinical research.
authors.affiliation: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, USA.
authors.forename: Zackary A
authors.initials: ZA
authors.lastname: Cope
authors.affiliation: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, USA.|Research Service, VA San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Halberstadt
authors.affiliation: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, USA.|Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
authors.forename: Jordy
authors.initials: J
authors.lastname: van Enkhuizen
authors.affiliation: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, USA.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Flynn
authors.affiliation: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Breier
authors.affiliation: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, USA.
authors.forename: Neal R
authors.initials: NR
authors.lastname: Swerdlow
authors.affiliation: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, USA.|Research Service, VA San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Geyer
authors.affiliation: Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, USA. jaredyoung@ucsd.edu.|Research Service, VA San Diego Healthcare System, San Diego, CA, USA. jaredyoung@ucsd.edu.
authors.forename: Jared W
authors.initials: JW
authors.lastname: Young
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology*; D013759:Dronabinol / Q000494:pharmacology; D007175:Impulsive Behavior / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology*
chemical_list: D063386:Cannabinoid Receptor Agonists; D013759:Dronabinol
keywords: 5-CSRTT; 5C-CPT; Attention; Impulsivity; Response inhibition; Temporal perception; Tetrahydrocannabinol