Pharmacokinetic and pharmacodynamic analysis of d-amphetamine in an attention task in rodents

Behav Pharmacol. 2018 Sep;29(6):551-556. doi: 10.1097/FBP.0000000000000409.

Abstract

Amphetamine is a common therapeutic agent for alleviating the core symptoms associated with attention-deficit hyperactivity disorder (ADHD) in children and adults. The current study used a translational model of attention, the five-choice serial reaction time (5-CSRT) procedure with rats, to examine the time-course effects of d-amphetamine. Effects of different dosages of d-amphetamine were related to drug-plasma concentrations, fashioned after comprehensive pharmacokinetic/pharmacodynamic assessments that have been employed in clinical investigations. We sought to determine whether acute drug-plasma concentrations that enhance performance in the 5-CSRT procedure are similar to those found to be therapeutic in patients diagnosed with ADHD. Results from the pharmacokinetic/pharmacodynamic assessment indicate that d-amphetamine plasma concentrations associated with improved performance on the 5-CSRT procedure overlap with those that have been reported to be therapeutic in clinical trials. The current findings suggest that the 5-CSRT procedure may be a useful preclinical model for predicting the utility of novel ADHD therapeutics and their effective concentrations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Attention / drug effects*
  • Choice Behavior / drug effects
  • Conditioning, Operant / drug effects*
  • Dextroamphetamine / blood*
  • Dextroamphetamine / pharmacology*
  • Dose-Response Relationship, Drug
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Time Factors

Substances

  • Dextroamphetamine