- Atomoxetine dose-dependently impaired visual signal detection, especially in low-attentive rats, with high doses generally reducing discrimination performance.
- Low-dose d-amphetamine improved target discrimination only in rats with lower baseline attention, demonstrating baseline-dependent effects.
- Methylphenidate failed to significantly enhance attention, instead increasing guessing, indicating contrasting effects of DA versus NA transporter blockade.
Psychopharmacology (Berl). 2026 Aug 5. doi: 10.1007/s00213-026-07131-7. Online ahead of print.
ABSTRACT
RATIONALE: Attention-deficit/hyperactivity disorder (ADHD) is associated with executive dysfunction involving inattention and impulsivity, with evidence of disrupted functional expression of the dopamine and noradrenaline transporters.
OBJECTIVE: We investigated the dose-dependent modulation of anti-ADHD drugs on selective and sustained visual attention in low-, mid- and high-attention phenotypes. Two mathematical approaches, signal detection theory and theory of visual attention were applied to further characterise the effects and mechanisms.
METHODS: Rats were trained to detect and respond to the presence or absence of a visual target to obtain food reward on a signal detection task. After attentional performance stabilised, the indirect catecholamine agonist, d-amphetamine (0.1; 0.2; 0.4 mg/kg), the dopamine (DA) and noradrenaline (NA) reuptake inhibitor methylphenidate (0.3; 1; 3 mg/kg), and the NA reuptake inhibitor atomoxetine (0.1; 0.3; 1 mg/kg), were administered systemically.
RESULTS: Low-dose d-amphetamine produced baseline-dependent effects on attention, improving target discrimination only in rats with lower attentive performance, whereas methylphenidate did not significantly improve attention but increased guessing. In contrast, low-dose atomoxetine selectively impaired attention in low-attentive subjects, whereas high-dose atomoxetine generally impaired discrimination performance. All three drugs had expected effects on motor response output.
CONCLUSIONS: As well as demonstrating baseline-dependent effects of amphetamine on visual attention, the findings for methylphenidate and atomoxetine suggest important, apparently opposing effects on visual signal detection performance produced via blockade of the DA and NA transporters. The deleterious effects of atomoxetine on performance were especially noteworthy in view of its use as a treatment in ADHD.
PMID:42554847 | DOI:10.1007/s00213-026-07131-7
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