Sleep electroencephalographic response to muscarinic and serotonin1A receptor probes in patients with major depression and in normal controls

Biol Psychiatry. 1998 Jul 1;44(1):21-33. doi: 10.1016/s0006-3223(97)00551-9.


Background: To test the hypothesis that depression is associated with an increased ratio of cholinergic to serotonergic neurotransmission, we compared the effects of pilocarpine, a muscarinic agonist, and ipsapirone, a serotonin (5-HT)1A agonist, on electroencephalographic (EEG) sleep in depressed and healthy subjects. We hypothesized, adopting the reciprocal interaction model, that the effects on REM sleep of these probes within the same individuals are negatively correlated and unmask neurobiological changes in depression.

Methods: Polysomnographic recordings were obtained in 12 unmedicated patients with a current major depression and 12 normal controls. They received placebo, pilocarpine 25 mg, or ipsapirone 10 mg (orally, 15 min before bedtime, after premedication with the peripheral anticholinergic probanthine 30 mg, double blind, counterbalanced) on three occasions.

Results: Pilocarpine shortened and ipsapirone prolonged REM latency equally in both groups. These effects were not correlated. Pilocarpine decreased slow-wave sleep and EEG delta power during the first nonREM episode more in controls than in patients, and enhanced EEG sigma power equally in both groups. Ipsapirone had no significant effects on EEG power.

Conclusion: These data do not support the postulate of muscarinic receptor up-regulation and 5-HT1A receptor down-regulation in depression. The significance of blunted delta power suppression in patients following pilocarpine warrants further investigations.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Depressive Disorder / diagnosis
  • Depressive Disorder / physiopathology*
  • Double-Blind Method
  • Down-Regulation
  • Electroencephalography / drug effects*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pilocarpine / pharmacology*
  • Placebos
  • Polysomnography / drug effects
  • Pyrimidines / pharmacology*
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / physiology*
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Serotonin Receptor Agonists / pharmacology*
  • Sleep / drug effects
  • Sleep / physiology*
  • Sleep, REM / drug effects
  • Sleep, REM / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Up-Regulation


  • Placebos
  • Pyrimidines
  • Receptors, Muscarinic
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • Pilocarpine
  • ipsapirone