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 β_1/2 (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 β_1/2 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.

Antagonist; Arousal; Attention; Impulsivity; Noradrenaline; Rodent continuous performance test.