Effects of atomoxetine and methylphenidate on performance of a lateralized reaction time task in rats.

ABSTRACT

RATIONALE The ability to detect unpredictable cues can involve stimulus-elicited orienting of attention (bottom-up processing); however, in many settings, target onset is partially predictable, meaning that subjects can benefit from the rule-guided, endogenous control of attention (top-down processing). Noradrenaline has been implicated in attention per se, but it is not clear whether it differentially participates in these two dimensions of attentional function. OBJECTIVES: We sought to examine the effects of selective or nonselective inhibitors of noradrenaline reuptake on different modes of attentional performance in rats. MATERIALS AND METHODS: Adult male Long-Evans rats were trained to perform a lateralized reaction time task where a variable-duration preparatory period preceded delivery of a visual target stimulus. Atomoxetine (1 mg/kg, i.p.) or methylphenidate (0.32 mg/kg, i.p.) were administered before sessions in which the preparatory period was systematically varied. RESULTS: When the preparatory time was brief (0.2 s), response times were significantly longer than when the preparatory time was long (1.0 s), suggesting that rats were able to orient their attention before target onset when the longer period was imposed. Atomoxetine differentially modulated performance in these two conditions, improving response accuracy when a long preparatory period was imposed but impairing accuracy when the preparatory time was made brief. Methylphenidate did not differentially affect responding under the two conditions. CONCLUSIONS: These data suggest that selective inhibition of the noradrenaline transporter may specifically benefit attentional performance of tasks that permit the controlled recruitment of attention, rather than during tests of pure stimulus-driven attention.