Assessing attention and impulsivity in the variable stimulus duration and variable intertrial interval rodent continuous performance test schedules using dopamine receptor antagonists in female C57BL/6JRj mice.

RATIONALE: Dopaminergic dysfunction is implicated in disorders of impulsivity and inattention. The rodent continuous performance test (rCPT) has been used to quantify changes in attention and impulsivity. OBJECTIVE: To examine the roles of dopamine receptors in attention and impulsivity behaviours measured in the rCPT variable stimulus duration (vSD) and the variable intertrial interval schedules (vITI) using DA receptor antagonists. METHODS: Two cohorts of 35 and 36 female C57BL/6JRj mice were examined separately in the rCPT, vSD, and vITI schedules, respectively. Both cohorts received antagonists of the following receptors: D1/5 (SCH23390, SCH: 0.01, 0.02, 0.04 mg/kg) and D2/3 (raclopride, RAC 0.03, 0.10, 0.30 mg/kg) in consecutive balanced Latin square designs with flanking reference measurements. The antagonists were subsequently examined for effects on locomotor activity. RESULTS: SCH showed similar effects in both schedules, and the effects were reference-dependent in the vITI schedule. SCH reduced responding, but improved response accuracy, impulsivity, discriminability, and locomotor activity. RAC showed mixed effects on responsivity, but improved accuracy and discriminability. The discriminability improvement was driven by an increase in hit rate in the vITI schedule and a reduction in false alarm rate in the vSD schedule. RAC also decreased locomotor activity. CONCLUSION: Both D1/5 and D2/3 receptor antagonism reduced responding, but the outcome on discriminability differed, stemming from individual effects on hit and false alarm rate, and the weight of omissions within the calculation. The effects of SCH and RAC suggest that endogenous DA increases responding and impulsivity, but reduces accuracy and shows mixed effects on discriminability.

Assessing attention and impulsivity in the variable stimulus duration and variable intertrial interval rodent continuous performance test schedules using noradrenaline receptor antagonists in female C57BL/6JRj mice.

RATIONALE: Noradrenergic dysfunction is associated with disorders of impulsivity and inattention. The rodent continuous performance test (rCPT) quantifies changes in attention and impulsivity. OBJECTIVE: To use NA receptor antagonists to examine the roles of NA on attention and impulsivity behaviours measured in the rCPT variable stimulus duration (vSD) and the variable intertrial interval (vITI) schedules. METHODS: Two cohorts of 36 female C57BL/6JRj mice were examined separately in the rCPT vSD and vITI schedules. Both cohorts received antagonists of the following adrenoceptors: α1 (doxazosin, DOX: 1.0, 3.0, 10.0 mg/kg), α2 (yohimbine, YOH: 0.1, 0.3, 1.0 mg/kg), and ß1/2 (propranolol, PRO: 1.0, 3.0, 10.0 mg/kg) in consecutive balanced Latin square designs with flanking reference measurements. The antagonists were subsequently examined for effects on locomotor activity. RESULTS: DOX showed similar effects in both schedules, improving discriminability and accuracy, and reducing responding and impulsivity, and DOX also reduced locomotor activity. YOH showed prominent effects in the vSD schedule to increase responding and impulsivity, while impairing discriminability and accuracy. YOH did not affect locomotor activity. PRO increased responding and impulsivity, decreased accuracy, but did not affect discriminability or locomotor activity. CONCLUSION: Antagonism of α2 or ß1/2 adrenoceptors caused similar increases in responding and impulsivity and worsened attentional performance, while α1 adrenoceptor antagonism showed the opposite effects. Our results suggest that endogenous NA exerts bidirectional control of most behaviours in the rCPT. The parallel vSD and vITI studies showed a substantial overlap in effects, but also some differences that indicate differing sensitivity towards noradrenergic manipulations.

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.

Gabor patterns as stimuli in a rodent visual attention task.

BACKGROUND: Gabor patterns are defined as the product of a sinusoid function and a Gaussian envelope and are commonly used in visual and attentional research due to their ability to selectively stimulate the primary visual cortex. The aim of this study was to investigate whether Gabor patterns can be used as visual stimuli in the rodent continuous performance test (rCPT), a newly developed task to study attentional function and impulsivity. METHODS: Sixteen male C57BL/6 J mice were trained in the rCPT using Gabor patterns as visual stimuli and their performance was compared to sixteen mice that were trained using traditional high-contrast pattern stimuli. Mice were compared during training, baseline, and a variable stimulus duration probe. RESULTS: The Gabor pattern group required more training sessions to reach criteria than the group with high-contrast patterns. At baseline, the Gabor pattern group showed a higher false alarm rate and a lower discriminability index. As task difficulty increased during the variable stimulus duration probe, differences between groups became more pronounced. Specifically, the Gabor pattern group showed decreased hit rate and discriminability index, as well as increased false alarm rate and premature responses compared to the high-contrast pattern group. CONCLUSION: This feasibility study showed that it is possible to use Gabor patterns as visual stimuli in the rCPT, although it increases task demands. We discuss the differences between Gabor patterns and high-contrast patterns in the context of translatability of animal models in visual and cognitive research and give two examples of applicability.