Differential effects of ADHD medications on impulsive action in the mouse 5-choice serial reaction time task

Aberrant impulsivity is found in a number of psychiatric disorders including attention deficit hyperactivity disorder (ADHD). The 5-choice serial reaction time task (5-CSRTT) is a paradigm commonly used to assess impulsive control. We recently developed a protocol to habituate mice to a variable intertrial interval (vITI) schedule before assessing pharmacological effects on "waiting" impulsivity. This study aimed to develop on that initial investigation by testing the effects of three conventional ADHD medications. Consistent premature response rates were achieved in male C57BL/6 J mice in the first week out of 15 vITI (5-, 10- or 15-s) days (four training days followed by one drug treatment day per week for three weeks) before each drug study commenced. The effects of atomoxetine (1, 3 mg/kg), methylphenidate (1, 2 mg/kg) and guanfacine (0.03, 0.1 mg/kg) were investigated using a Latin-square design. High- and low-impulsive subgroups were determined based on initial training day data before the drug studies initiated. Both 1 and 3 mg/kg atomoxetine reduced premature responding at the 10- (P < 0.001, P < 0.05) and 15-s (P < 0.001) lengths. 2 mg/kg methylphenidate increased impulsive action at the longest 15-s ITI (P < 0.05). Guanfacine exerted no effects on premature responding rates at any dose or ITI. Impulsive subgrouping did not reveal any specific drug by subgroup effects. This study indicates that these current ADHD medications have differential effects on impulsive action. In summary, this protocol is a useful preclinical model for testing potential treatments for disorders with dysfunctional impulsive control.