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

Jonathan M. Slezak, Melanie Mueller, George Ricaurte, Jonathan L. Katz

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)551-556
Number of pages6
JournalBehavioural Pharmacology
Volume29
Issue number6
DOIs
StatePublished - Sep 1 2018

Keywords

  • attention
  • attention-deficit hyperactivity disorder
  • d-amphetamine
  • five-choice serial reaction time
  • pharmacokinetics
  • rat
  • time course

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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