Elsevier

Biological Psychiatry

Volume 57, Issue 2, 15 January 2005, Pages 192-195
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2004.11.004Get rights and content

Background

Stimulation of α2-adrenergic receptors (α2-ARs) in the prefrontal cortex (PFC) has a beneficial effect on working memory and attentional regulation in monkeys. α2-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 α2-ARs in the PFC are involved in the neural mechanisms underlying regulation of locomotor activity.

Methods

The α2-adrenergic antagonist yohimbine was infused 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 α2-ARs, not because of nonspecific factors such as cortical damage by drug administration.

Conclusions

The present study suggests that α2-ARs in the dlPFC are involved in inhibitory control of locomotor activity.

Section snippets

Subjects

Two young monkeys (Macaca mulatta, female, 2 years old) were used. They were housed individually in custom-made cages (80 cm × 80 cm × 90 cm, length × width × height) and maintained on a 12 hr-light/12 hr-dark cycle at a temperature of 25 ± 2°C. Food and water were available ad libitum. The monkeys were cared for in accordance with the Guiding Principles for the Care and the Use of Laboratory Animals issued by the National Institutes of Health in 1996. This study was approved and monitored by

Results

A total of 6 bilateral, symmetric infusions with yohimbine were carried out in the dlPFC, 3 infusions in each monkey. The cortical area and reconstructed sites for infusion are shown in the inset of Figure 1. All of the 6 infusions were effective for induction of locomotor hyperactivity (Figure 1A and B). Each monkey showed a dramatic increase in daily locomotion during the 8-day administration of yohimbine (Figure 1B; p < .01 for during infusion vs. before infusion, Mann-Whitney U-test).

Discussion

The neurobiological base for hyperactivity seen in ADHD is still unknown. Locomotor hyperactivity could have multiple neural origins. Many studies indicate that hyperactivity in ADHD involves dopaminergic mechanisms in the striatum and the prefrontal cortex (for review, see Levy and Swanson 2001). The present study provides the first evidence that α2-ARs in the monkey’s dlPFC may be involved in neural mechanisms regulating locomotor activity and offers a hypothesis that down-regulation or

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