THE 5-HT1A AGONIST IPSAPIRONE ENHANCES EEG SLOW-WAVE ACTIVITY IN HUMAN SLEEP AND PRODUCES A POWER SPECTRUM SIMILAR TO 5-HT2 BLOCKADE

The REM sleep-suppressing effect of postsynaptic 5-HT1A stimulation ha s been well established. Here we investigate the effects of the 5-HT1A agonist ipsapirone (10 and 20 mg) on sleep EEG power spectra during n on-REM sleep in nine healthy humans. At tile lower dose, slow wave act ivity (SWA; EEG power in the delta (1-4.5 Hz) range) was significantly enhanced. At the higher dose, where side-effects occurred, the enhanc ement in SWA-was not significant. The spectral profile was characteriz ed by a bimodal increase of power in the lower delta and in the theta (5-8 Hz) frequencies, and by troughs at 4 Hz and at 11 Hz, a pattern c ompellingly similar to that reported for a 5-HT2 antagonist (seganseri n). We propose that the spectral data following the lower ipsapirone d ose reflect a net decrease of neuronal activity at 5-HT2 receptors, me diated through stimulation of somatodendritic autoreceptors in the rap he nuclei (presynaptic) and/or through stimulation of postsynaptic 5-H T1A receptors colocalized with 5-HT2 receptors. The spectral non-REM s leep EEG profile might be used to investigate central 5-HT function in humans.