Locomotor hyperactivity induced by blockade of prefrontal cortical α2-adrenoceptors in monkeys

Background: Stimulation of alpha(2)-adrenergic receptors (alpha(2)-ARs) in the prefrontal cortex (PFC) has a beneficial effect on working memory and attentional regulation in monkeys. alpha(2)-adrenergic agonists like clonidine and guanfacine have been used experimentally and clinically for the treatment of attention deficit and hyperactivity disorder (ADHD). However, it is unknown if alpha(2)-ARs in the PFC are involved in the neural mechanisms underlying regulation of locomotor activity. Methods: The alpha(2)-adrenergic antagonist yohimbine was h fused bilaterally and chronically into the dorsolateral PFC (dlPFC) in two monkeys, using mini-osmotic pumps. Spontaneous locomotor activity was measured continuously before, during and after drug administration, using an activity monitor. Results: The monkeys exhibited a dramatic increase in motoric activity during infusion of yohimbine into the dlPFC. Similar treatment with saline was without effect. Thus, the locomotor hyperactivity was due to blockade of alpha(2)-ARs, not because of nonspecific factors such as cortical damage by drug administration. Conclusions: The present study suggests that alpha(2)-ARs in the dlPFC are involved in inhibitory control of locomotor activity.