TY - JOUR

T1 - Relationship between two forms of impulsivity in mice at baseline and under acute and sub-chronic atomoxetine treatment

AU - Kyriakidou, Maria

AU - Caballero-Puntiverio, Maitane

AU - Andreasen, Jesper T.

AU - Thomsen, Morgane

N1 - Publisher Copyright: © 2023 The Authors

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Atomoxetine

KW - Delay discounting

KW - Impulsivity

KW - Impulsivity forms

KW - Premature responding

KW - Rodent continuous performance test

U2 - 10.1016/j.pnpbp.2023.110841

DO - 10.1016/j.pnpbp.2023.110841

M3 - Journal article

C2 - 37586638

AN - SCOPUS:85168817737

VL - 127

JO - Progress in Neuro-Psychopharmacology & Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology & Biological Psychiatry

SN - 0278-5846

M1 - 110841

ER -