Effects of selective dopamine D4 receptor antagonist, L-741,741, on sleep and wakefulness in the rat

The influence of the dopamine system upon sleep/wake states is not fully understood. To date, the role of dopamine D4 receptor has not been studied. The aim of this work is to study the influence of dopamine D4 receptor upon sleep/wake states in male rats. Male Wistar rats were implanted with electroencephalography and electromyography electrodes for sleep recording. Sleep/wake times were compared in rats first treated with control solution (vehicle) and the day after treated with a potent and highly selective D4 dopamine receptor antagonist. L-741,741 (1.5, 3, 6 mg/kg) or vehicle solution (10% DMSO in saline) was administered intraperitoneally at the beginning of the light period. Subsequently, 3 h of polysomnography were recorded and sleep-wake parameters evaluated. For statistical comparisons, Wilcoxon ranges test was performed. L-741,741 (1.5 mg/kg) only increased Light Slow Wave Sleep (SWS). 3 mg/kg enhanced Quiet Waking (QW) increasing number of episodes, whereas Active Waking (AW) was reduced decreasing mean episode duration. 6 mg/kg reduced number of episodes of Deep SWS and increased its latency. Light SWS was decreased reducing number of episodes and their duration. Total time spent asleep was reduced and time spent in AW was increased. REM latency was increased. These results suggest a role for D4 receptors in the regulation of wake and sleep. (c) 2005 Elsevier Inc. All rights reserved.