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

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.