Perfusion of a 5-HT_1A Antagonist in the Cat DRN
Increases Wakefulness and Extracellular 5-HT Level in DRN
Alvhild A. Bjørkum^1,2, Robert E. Strecker², Chiara M. Portas^1,2,
Tarja Porkka-Heiskanen², Mahesh Thakkar²
and Robert W. McCarley^2
1Department of Physiology, University of Bergen, Norway

²Department of Psychiatry, VA Medical Center/Harvard Medical School, Brockton, MA, USA

The serotonergic system is involved in modulation of sleep and waking and shows a state dependent activity: waking (W) > slow wave sleep (SWS) > rapid eye movement sleep (REM). Our laboratory has recently shown that microdialysis perfusion of a 5-HT_1A receptor agonist 8-OH-DPAT in the DRN decreases serotonin (5-HT) release and increases REM sleep in the freely moving cat. We now demonstrate that DRN perfusion of a 5-HT_1A antagonist (p-MPPI) produces an increase in the extracellular 5-HT levels in the DRN paralleled by an increase in waking as measured by polygraphic techniques. These results are compatible with the blockade of the inhibitory 5-HT_1A somatodendritic autoreceptors on 5-HT neurons leading to increased serotonergic activity and a corresponding increase in wakefulness.