SLEEP ELECTROENCEPHALOGRAPHIC RESPONSE TO MUSCARINIC AND SEROTONIN(1A) RECEPTOR PROBES IN PATIENTS WITH MAJOR DEPRESSION AND IN NORMAL CONTROLS

Background: To test the hypothesis that depression is associated with art increased ratio of cholinergic to serotonergic neurotransmission, we compared the effects of pilocarpine, a muscarinic agonist, and ipsa pirone, a serotonin (5-HT)(1A) agonist, on electroencephalographic (EE G) sleep in depressed and healthy subjects. We hypothesized, adopting the reciprocal interaction model, that the effects on REM sleep of the se probes within the same individuals are negatively correlated and un mask neurobiological changes in depression. Methods: Polysomnographic recordings were obtained in 12 unmedicated patients with a current maj or depression and 12 normal controls. They received placebo, pilocarpi ne 25 mg, or ipsapirone 10 mg (orally, 15 min before bedtime, after pr emedication with the peripheral anticholinergic probanthine 30 mg, dou ble blind, counter-balanced) on three occasions. Results: Pilocarpine shortened and ipsapirone prolonged REM latency equally in both groups. These effects were not correlated Pilocarpine decreased slow-wave sle ep and EEG delta power during the first nonREM episode more in control s than in patients, and enhanced EEG sigma power equally in both group s. Ipsapirone had no significant effects on EEG power. Conclusion: The se data do not support the postulate of muscarinic receptor up-regulat ion and 5-MT1A receptor down-regulation in depression. The significanc e of blunted delta power suppression in patients following pilocarpine warrants further investigations. Biol Psychiatry 1998;44: 21-33.