Human sleep EEG following the 5-HT1A antagonist pindolol: possible disinhibition of raphe neuron activity.
The sleep electroencephalogram (EEG) was used to assay central effects of pindolol (10 and 30 mg p.o.), a mixed beta(1/2)-adrenoceptor/5-hydroxytryptamine (5-HT)(1A/1B) receptor blocker, in humans. Compared to placebo, pindolol produced a dose-related suppression of rapid-eye-movement (REM) sleep, including a prolongation of REM latency, and a decrease of REM time and REM density. At the higher dose, it also reduced EEG spectral power during non-REM sleep in portions of the delta, theta, and alpha frequencies (1.125-5.125 Hz, 7.125-9.625 Hz). By contrast, betaxolol (20 mg p.o.), a selective beta1-antagonist devoid of serotonergic affinity, affected neither REM sleep nor EEG power. REM sleep is, in part, under the inhibitory control of serotonergic neurons projecting from the dorsal raphe nucleus to pontine cholinergic/cholinoceptive cells. The EEG power spectrum induced by pindolol tended to be opposite to what has previously been reported for ipsapirone, a 5-HT1A agonist. Therefore, the present data, tentatively, are consistent with the contention that pindolol inhibits, possibly selectively, somatodendritic 5-HT1A autoreceptors in humans and may antagonize self-inhibition of midbrain raphe nuclei 5-HT neurons.
Seifritz
E
E
Mental Health Clinical Research Center, Department of Psychiatry, University of California at San Diego, USA. eseifritz@ucsd.edu
Stahl
S M
SM
Gillin
J C
JC
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D015784:Betaxolol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D006801:Humans; D008297:Male; D008875:Middle Aged; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000502:physiology; D010869:Pindolol / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects* / Q000502:physiology*; D012894:Sleep Stages / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D012702:Serotonin Antagonists; D010869:Pindolol; D015784:Betaxolol