ADHD medication and the inverted U-shaped curve: A pharmacological study in female mice performing the rodent Continuous Performance Test (rCPT)
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ADHD medication and the inverted U-shaped curve : A pharmacological study in female mice performing the rodent Continuous Performance Test (rCPT). / Caballero-Puntiverio, M; Lerdrup, L S; Arvastson, L; Aznar, S; Andreasen, J T.
In: Progress in Neuro-Psychopharmacology & Biological Psychiatry, Vol. 99, 109823, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - ADHD medication and the inverted U-shaped curve
T2 - A pharmacological study in female mice performing the rodent Continuous Performance Test (rCPT)
AU - Caballero-Puntiverio, M
AU - Lerdrup, L S
AU - Arvastson, L
AU - Aznar, S
AU - Andreasen, J T
N1 - Copyright © 2019 Elsevier Inc. All rights reserved.
PY - 2020
Y1 - 2020
N2 - BACKGROUND: The rodent Continuous Performance Test (rCPT) is an analogue of human CPTs where mice have to discriminate between target and non-target stimuli. The rCPT offers a readout of attentional performance and impulsive behaviour. This study aimed to determine if female C57BL/6 J mice could be trained in the rCPT since previously published rCPT studies have only used male mice and to study whether the effects of methylphenidate (MPH), atomoxetine (ATX), and dexamphetamine (AMPH) on attention and impulsivity depend on baseline (reference) levels of performance.METHODS: 48 female mice underwent rCPT training. Effects of MPH (1, 2, and 3 mg/kg), ATX (1, 3, and 5 mg/kg) and AMPH (0.3, 0.6, and 1 mg/kg) were assessed in a variable stimulus duration probe. Drugs were administered intraperitoneally and sequentially tested following a Latin-square design. Data were analysed using a repeated measurements mixed effect model and reference-dependent effects were studied.RESULTS: ATX and AMPH improved performance as seen by increases in discriminability. These improvements were a result of a decreased false-alarm rate. AMPH showed a reference-dependent effect, improving the task performance of low-performing mice and decreasing the performance of high-performing mice. MPH also showed this reference-dependent effects, albeit to a lesser extent. ATX and AMPH decreased premature responses and increased response criterion, but no reference-dependent effects were observed for these parameters.CONCLUSION: This study presents a novel method to analyse baseline-dependent effects. It shows that the rCPT can be successfully used in pharmacological studies in female mice and demonstrates that the effect of ADHD medication is in line with the inverted U-shape theory of performance-arousal relationship.
AB - BACKGROUND: The rodent Continuous Performance Test (rCPT) is an analogue of human CPTs where mice have to discriminate between target and non-target stimuli. The rCPT offers a readout of attentional performance and impulsive behaviour. This study aimed to determine if female C57BL/6 J mice could be trained in the rCPT since previously published rCPT studies have only used male mice and to study whether the effects of methylphenidate (MPH), atomoxetine (ATX), and dexamphetamine (AMPH) on attention and impulsivity depend on baseline (reference) levels of performance.METHODS: 48 female mice underwent rCPT training. Effects of MPH (1, 2, and 3 mg/kg), ATX (1, 3, and 5 mg/kg) and AMPH (0.3, 0.6, and 1 mg/kg) were assessed in a variable stimulus duration probe. Drugs were administered intraperitoneally and sequentially tested following a Latin-square design. Data were analysed using a repeated measurements mixed effect model and reference-dependent effects were studied.RESULTS: ATX and AMPH improved performance as seen by increases in discriminability. These improvements were a result of a decreased false-alarm rate. AMPH showed a reference-dependent effect, improving the task performance of low-performing mice and decreasing the performance of high-performing mice. MPH also showed this reference-dependent effects, albeit to a lesser extent. ATX and AMPH decreased premature responses and increased response criterion, but no reference-dependent effects were observed for these parameters.CONCLUSION: This study presents a novel method to analyse baseline-dependent effects. It shows that the rCPT can be successfully used in pharmacological studies in female mice and demonstrates that the effect of ADHD medication is in line with the inverted U-shape theory of performance-arousal relationship.
U2 - 10.1016/j.pnpbp.2019.109823
DO - 10.1016/j.pnpbp.2019.109823
M3 - Journal article
C2 - 31765714
VL - 99
JO - Progress in Neuro-Psychopharmacology & Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology & Biological Psychiatry
SN - 0278-5846
M1 - 109823
ER -
ID: 232912294