On the improvement of inhibitory response control and visuospatial attention by indirect and direct adrenoceptor agonists

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Abstract
Rationale The clinical efficacy of the monoamine and noradrenaline transporter inhibitors methylphenidate and atomoxetine in attention deficit/hyperactivity disorder implicates noradrenergic neurotransmission in modulating inhibitory response control processes. Nonetheless, it is unclear which adrenoceptor subtypes are involved in these effects. Objectives The present study aimed at investigating the effects of adrenoceptor agonists on inhibitory response control as assessed in the rodent 5-choice serial reaction time task, a widely used translational model to measure this executive cognitive function. Results Consistent with the previous reported effects of atomoxetine, the noradrenaline transporter inhibitor desipramine improved inhibitory response control, albeit the effect size was smaller compared to that of atomoxetine. Methylphenidate exerted a bimodal effect on inhibitory response control. Interestingly, the preferential β2-adrenoceptor agonist clenbuterol improved inhibitory response control. Moreover, clenbuterol improved visuospatial attention in the task, an effect that was also observed with the preferential β1-adrenoceptor agonist dobutamine. By contrast, although the preferential α1-adrenoceptor and α2-adrenoceptor agonists (phenylephrine and clonidine, respectively) and the non-selective β-adrenoceptor agonist (isoprenaline) were found to alter inhibitory response control, this was probably secondary to the simultaneous increments in response latencies and omissions observed at effective doses. Conclusions Taken together, these findings further strengthen the notion of noradrenergic modulation of inhibitory response control and attentional processes and particularly reveal the involvement of β2-adrenoceptors therein.

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