Sleep and waking following microdialysis perfusion of the selective 5-HT1A receptor antagonist p-MPPI into the dorsal raphe nucleus in the freely moving rat.

The aim of this study was to examine the involvement of the dorsal raphe nucleus (DRN) presynaptic serotonergic 5-HT1A autoreceptors on sleep and waking parameters, in particular rapid eye movement (REM) sleep. In a previous study, the systemic administration of the selective 5-HT1A receptor antagonist p-MPPI reduced REM sleep in a dose-dependent manner suggesting a blockade of the 5-HT1A autoreceptors. In the present study, a blockade by microdialysis perfusion of 10 microM and 100 microM of p-MPPI for 7 h into the DRN in freely behaving rats influenced vigilance state only to a small extent. The administration of 10 microM of p-MPPI induced a reduction of total REM sleep mainly due to a suppression of REM sleep during the third 2 h period of the recording of sleep and waking. Perfusion of 100 microM of p-MPPI decreased total transition type sleep (TRANS) but the effect on REM sleep did not reach significance. There was no change in waking or slow wave sleep (SWS) following any of the doses. The data suggest that 5-HT1A receptor-mediated mechanisms in the DRN may be only moderately important in the serotonergic modulation of REM sleep.