Contrasting effects of d-amphetamine and atomoxetine on measures of impulsive action and choice

Pharmacol Biochem Behav. 2021 Aug:207:173220. doi: 10.1016/j.pbb.2021.173220. Epub 2021 Jun 24.

Abstract

Amphetamine (AMP) and atomoxetine (ATX) represent two of the most widely studied drug treatments used in the investigation of impulsive behaviour. While both drugs have relatively well defined effects in tests designed to investigate impulsive action (e.g. 5-choice task; 5-CSRTT), the effects of both drugs in tests of impulsive choice (e.g. delay discounting) are less consistent. In the present study both AMP and ATX were tested in a rodent gambling task (rGT) and delay discounting in rats separately trained to either an ascending or descending delay schedule. Effects of both drugs were compared to measures of impulsive action (premature (PREM) responses) and perseverative (PSV) responses measured in the 5-choice and rGT tasks. Consistent with previous studies, AMP (0.1-1 mg/kg) increased both PREM and PSV responses, and ATX (0.5-2 mg/kg) reduced both measures in the 5-choice and rGT tasks. At equivalent doses ATX had no reliable effect on choice behaviour in either the rGT or delay discounting suggesting a null effect of this drug on impulsive choice and risky decision making. The effects of AMP were more complex, with a subtle shift in preference to a low risk (P1) choice in the rGT, and an effect on discounting that was unrelated to reinforcer value, but instead dependent on delay sequence and baseline choice preference. One aspect to these outcomes is to highlight the importance of multiple methodological factors when assessing drug effects on complex behaviours such as impulsive choice, and question what are the most appropriate test conditions under which to examine these drugs on discounting.

Keywords: 5-Choice serial reaction time task; Amphetamine; Atomoxetine; Decisional impulsivity; Delay discounting; Gambling task; Impulsivity; Rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Animals
  • Atomoxetine Hydrochloride / pharmacology*
  • Behavior, Animal / drug effects
  • Choice Behavior / drug effects*
  • Conditioning, Operant
  • Decision Making / drug effects
  • Delay Discounting / drug effects
  • Dextroamphetamine / pharmacology*
  • Gambling / psychology
  • Impulsive Behavior / drug effects*
  • Male
  • Rats
  • Rats, Long-Evans
  • Reaction Time / drug effects

Substances

  • Adrenergic Uptake Inhibitors
  • Atomoxetine Hydrochloride
  • Dextroamphetamine