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Blockade of noradrenaline re-uptake sites improves accuracy and impulse control in rats performing a five-choice serial reaction time tasks

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Abstract

Rationale

Atomoxetine, reboxetine and methylphenidate all act at the noradrenaline transporter (NAT) and atomoxetine and methylphenidate are licensed for the treatment of ADHD. The five-choice serial reaction time task (5CSRTT) provides a valid model to study attention and impulsivity in rodents. Studies using this task have largely failed to demonstrate improvements in attention with atomoxetine and methylphenidate and reboxetine has not been investigated previously.

Objectives

The present study used modifications to the standard rat 5CSRTT and demonstrated that blockade of NAT improves attention and reduces premature responding.

Methods

Rats were trained in a fixed inter-trial interval (ITI), 5CSRTT then tested at baseline and under conditions to acutely challenge attention and/or impulse control following vehicle or atomoxetine (0.3 mg/kg, i.p.).

Results

Atomoxetine (0.3 mg/kg, i.p.) significantly improved impulse control under all conditions (p < 0.05) but had no significant effects on accuracy. To increase the attentional demands of the task, rats were re-baselined in a non-paced, variable ITI task where presentations of the stimuli were unpredictable. In the VITI task, atomoxetine (0.0–0.3 mg/kg, i.p.) induced a dose-dependent improvement in accuracy (p < 0.05) and reduction in premature responses (p < 0.05). Reboxetine (0.0–1.0 mg/kg, i.p.) and methylphenidate (1–10 mg/kg, p.o.) did not significantly improve accuracy in the whole population but median split analysis revealed a significant improvement with both drugs, as well as atomoxetine, in the poor performing animals (p < 0.05).

Conclusions

These data suggest that blockade of noradrenaline re-uptake sites is an important target in terms of enhancing both attention and impulse control.

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Acknowledgements

The author would like to thank Prof. David Nutt and Prof. Trevor Robbins for their valued discussion of this work, Sian Cundy for technical assistance and Nicholas Donnelly (Wellcome summer studentship) and Christian Wood (Nuffield summer studentship) for their help with running some of the experiments included in this manuscript. Funding for this research was provided by a Medical Research Council New Investigator grant (Ref: G0700980) awarded to E.S.J.R.

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The author of this manuscript has no conflict of interest.

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  1. School of Physiology and Pharmacology, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK

    Emma S. J. Robinson

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Correspondence to Emma S. J. Robinson.

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Robinson, E.S.J. Blockade of noradrenaline re-uptake sites improves accuracy and impulse control in rats performing a five-choice serial reaction time tasks. Psychopharmacology 219, 303–312 (2012). https://doi.org/10.1007/s00213-011-2420-3

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  • DOI: https://doi.org/10.1007/s00213-011-2420-3

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