Relationship between two forms of impulsivity in mice at baseline and under acute and sub-chronic atomoxetine treatment

RATIONALE: Impulsivity is a symptom of various mental disorders, including attention deficit hyperactivity disorder (ADHD), bipolar disorder, and addiction. Impulsivity is not a unitary construct, but is present in different forms, yet only a few rodent studies have explored the relationship between these forms within individual subjects.

OBJECTIVES: In this study, we compared behaviors representing two impulsivity forms, delay discounting (choice impulsivity) and premature responding (waiting impulsivity), within the same mice.

METHODS: C57BL/6J male mice were concurrently trained and tested in the delay discounting task and the rodent continuous performance test in a counterbalanced design. The effects of the ADHD medication atomoxetine were tested in both tasks, after both acute (0.3-5.0 mg/kg) and sub-chronic (0.3 mg/kg twice daily for seven days) administration.

RESULTS: There was no correlation between the two impulsivity forms at baseline. Acute atomoxetine treatment (1, 3, and 5 mg/kg) significantly reduced premature responding. Furthermore, sub-chronic treatment with 0.3 mg/kg of atomoxetine caused a stable decrease in premature responding. Atomoxetine had no significant effect on delay discounting after acute or sub-chronic administration, although the acute administration of 1 mg/kg showed a trend towards increasing delay discounting.

CONCLUSIONS: The present results support that delay discounting and premature responding represent two different forms of impulsivity that show dissimilar responses to atomoxetine treatment. The consistency with findings in humans lends support to the translatability of the results in mice.