Validation of a method to assess ADHD-related impulsivity in animal models

J Neurosci Methods. 2015 Aug 30:252:36-47. doi: 10.1016/j.jneumeth.2015.03.020. Epub 2015 Apr 1.

Abstract

Background: Response inhibition capacity (RIC), the ability to withhold instrumentally reinforced responses, is compromised in ADHD. Most standard methods for assessing RIC in rodents potentially confound motivational, motor, learning, and inhibitory processes, lack sensitivity to pharmacological treatment, and have unknown reliability.

New method: The fixed minimum interval (FMI) schedule of reinforcement and its associated analytical techniques are designed to dissociate inhibitory processes from incentive-motivational and timing processes. This study is aimed at validating the FMI as a method for assessing RIC in animal models. FMI performance was compared across different withholding requirements (0.5, 3, 6 and 21s), deprivation levels, reinforcement rates, and reinforcer magnitudes.

Results and comparison with existing methods: Motivational manipulations differentially affected estimates of incentive motivation but not the FMI-derived index of RIC, θ. Changes in the withholding requirement influenced timed IRTs in a manner consistent with extant timing theories. Individual estimates of RIC were resilient to prolonged changes in motivation but not to changes in FMI schedule. Results indicate that the FMI schedule is not vulnerable to the same limitations associated with existing methods for assessing RIC.

Conclusions: These results support the use of the FMI schedule and associated analytic techniques as tools for assessing RIC in animal models.

Keywords: ADHD; Fixed minimum interval schedule; Impulsivity; Incentive motivation; Response inhibition capacity; Temporal Regulation model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Attention Deficit Disorder with Hyperactivity / diagnosis*
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Disease Models, Animal*
  • Impulsive Behavior / physiology*
  • Inhibition, Psychological
  • Male
  • Probability
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time
  • Reinforcement Schedule
  • Reinforcement, Psychology
  • Reproducibility of Results