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Behav Brain Res. 2013 Jul 15;249:65-74. doi: 10.1016/j.bbr.2013.04.024. Epub 2013 Apr 24.

The effects of systemic and local microinjection into the central nervous system of the selective serotonin 5-HT6 receptor agonist WAY-208466 on sleep and wakefulness in the rat.

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Department of Pharmacology and Therapeutics, School of Medicine Clinics Hospital. Montevideo 11600, Uruguay.


The effects of WAY-208466, a selective 5-HT6 receptor agonist on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. Systemic administration of WAY-208466 during the light phase of the light-dark cycle significantly increased wakefulness (W) and reduced slow wave sleep (SWS), REM sleep (REMS) and the number of REMS periods. Pretreatment with the selective 5-HT6 receptor antagonist RO-399885 prevented the effects of the 5-HT6 receptor agonist on W, SWS and REMS. Direct infusion of WAY-208466 into the dorsal raphe nucleus, locus coeruleus, basal forebrain (horizontal limb of the diagonal band of Broca) or laterodorsal tegmental nucleus specifically decreased REMS without significantly altering W or SWS. In all instances the REMS suppression was dependent upon the reduction of REMS periods. The finding that WAY-208466 increases extracellular γ-aminobutyric acid (GABA) levels in the rat frontal cortex tends to suggest that the neurotransmitter could be involved in the 5-HT6 receptor agonist-induced disruption of the sleep-wake cycle. However, further studies are needed to resolve this issue.

[Indexed for MEDLINE]

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