Assessing the nature of premature responses in the rodent continuous performance test variable intertrial interval schedule using atomoxetine and amphetamine.

BACKGROUND: Rodent operant tests that include premature responses (PR) as a measure of impulsivity commonly use variable intertrial interval (vITI) schedules. The rodent continuous performance test (rCPT) is suitable for a vITI schedule. NEW METHOD: We optimised the analysis for a rCPT vITI schedule with intertrial intervals (ITIs) of 3, 6, and 12 s. Examining the nature of first (FiT) and following touches (FoT) to the blank screen led to a separate quantification of these two behaviours into the first touches level (%FiT) and the following-to-first touches ratio (FoT/FiT). RESULTS: FiTs occurred more frequently in the 12 s ITIs than at shorter ITIs. Within 12 s ITIs, %FiT was only moderately higher during the last half than the first half, suggesting that long ITIs have a minimal effect on impulsivity, but allow a longer time for its detection. %FiT and the FoT/FiT ratio were uncorrelated. %FiT was negatively correlated with response criterion (C) and uncorrelated with discriminability. Conversely, FoT/FiT ratio was negatively correlated with discriminability, without correlation to C. Atomoxetine decreased %FiT but did not affect FoT/FiT ratio. Amphetamine increased %FiT and decreased the FoT/FiT ratio. COMPARISON WITH EXISTING METHOD(S): The results suggest that %FiT is analogous to %PR in related tasks and is a more suitable measure of waiting impulsivity in the rCPT. FoT/FiT ratio is unrelated to %FiT. CONCLUSIONS: Long ITIs increase the detectability of, but has minimal effect on, waiting impulsivity. %FiT is analogous to %PR in related tasks, while the FoT/FiT ratio is a separate behaviour requiring further characterization.

ADHD medication and the inverted U-shaped curve: A pharmacological study in female mice performing the rodent Continuous Performance Test (rCPT).

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.