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

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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.
OriginalsprogEngelsk
Artikelnummer110841
TidsskriftProgress in Neuro-Psychopharmacology and Biological Psychiatry
Vol/bind127
Antal sider11
ISSN0278-5846
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The research was funded by the Independent Research Fund Denmark grant 8020-00110B (MT) and the Research Fund of the Mental Health Services - Capital Region of Denmark (MT). MK was supported by funding from the National Institutes of Health , National Institute on Alcohol Abuse and Alcoholism [grant number R01AA025071 ] (MT) while working on the manuscript. Funding agencies had no role in data interpretation or the decision to publish.

Publisher Copyright:
© 2023 The Authors

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