Effects of amphetamine and methylphenidate on attentional performance and impulsivity in the mouse 5-Choice Serial

Maitane Caballero-Puntiverio1, Ciarán Martin Fitzpatrick1, David Pd Woldbye2

  • 11 Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.

Abstract

Insights

This study examined how methylphenidate (MPH) and amphetamine (AMPH) affect attention deficit-hyperactivity disorder (ADHD) symptoms in mice using the 5-choice serial reaction time task (5-CSRTT). Results showed these ADHD medications improved accuracy in low-attentive mice but increased impulsivity.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Science

Background:

  • Limited research exists on conventional attention deficit-hyperactivity disorder (ADHD) medication effects in the mouse 5-choice serial reaction time task (5-CSRTT).
  • Previous rat studies on ADHD medications in the 5-CSRTT have produced inconsistent findings.

Purpose of the Study:

  • To investigate the acute effects of methylphenidate (MPH) and amphetamine (AMPH) on performance in the mouse 5-CSRTT.
  • To assess the impact of these medications on attention and impulsivity in a rodent model.

Main Methods:

  • Male C57Bl/6J mice were trained on a 5-CSRTT with a variable stimulus duration schedule.
  • Effects of varying doses of AMPH (0.25-1 mg/kg) and MPH (0.5-2.0 mg/kg) were evaluated for accuracy, omissions, and premature responses.
  • Mice were categorized into high/low attentive (HA/LA) and high/low impulsive (HI/LI) subgroups based on saline performance.

Main Results:

  • Methylphenidate (MPH) and amphetamine (AMPH) improved discriminative accuracy in the low-attentive (LA) subgroup.
  • No significant accuracy improvements were observed in the high-attentive (HA) subgroup.
  • Both AMPH and MPH increased premature responses across all mice, with a notable increase in the low-impulsive (LI) subgroup for AMPH.

Conclusions:

  • Utilizing a variable stimulus duration and subgrouping (high/low attentive/impulsive) enhances the 5-CSRTT's sensitivity for detecting drug effects on attention and impulsivity.
  • This refined methodology provides a more nuanced understanding of stimulant medication actions in preclinical models of ADHD.