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 has been well established. Here we investigate the effects of the 5-HT1A agonist ipsapirone (10 and 20 mg) on sleep EEG power spectra during non-REM sleep in nine healthy humans. At the lower dose, slow wave activity (SWA; EEG power in the delta (1-4.5 Hz) range) was significantly enhanced. At the higher dose, where side-effects occurred, the enhancement in SWA was not significant. The spectral profile was characterized 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 compellingly similar to that reported for a 5-HT2 antagonist (seganserin). We propose that the spectral data following the lower ipsapirone dose reflect a net decrease of neuronal activity at 5-HT2 receptors, mediated through stimulation of somatodendritic autoreceptors in the raphe nuclei (presynaptic) and/or through stimulation of postsynaptic 5-HT1A receptors colocalized with 5-HT2 receptors. The spectral non-REM sleep EEG profile might be used to investigate central 5-HT function in humans.
Seifritz
E
E
Department of Psychiatry, UCSD, USA. eseifritz@ucsd.edu
Moore
P
P
Trachsel
L
L
Bhatti
T
T
Stahl
S M
SM
Gillin
J C
JC
D000328:Adult; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012016:Reference Values; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D012895:Sleep, REM / Q000502:physiology
D011743:Pyrimidines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; C043077:ipsapirone