Role of dorsal raphe nucleus serotonin 5-HT1a receptor in the regulation of REM sleep

Cholinergic neurons in the laterodorsal (LDT) and the pedunculopontine (PPT ) tegmental nuclei act to promote REM sleep (REMS). The predominantly gluta matergic neurons of the REMS-induction region of the medial pontine reticul ar formation are in turn activated by cholinergic cells, which results in t he occurrence of tonic and phasic components of REMS. All these neurons are inhibited by serotonergic (5-HT), noradrenergic, and presumably histaminer gic (H-2 receptor) and dopaminergic (D-2 and D-3 receptor) cells. 5-Hydroxy tryptamine-containing neurons in the dorsal raphe nucleus (DRN) virtually c ease firing when an animal starts REMS, consequently decreasing the release of 5-HT during this state. The activation of GABA, receptors is apparently responsible for this phenomenon. Systemic administration of the selective 5-HT1A receptor agonist 8-OHDPAT induces dose-dependent effects; i.e. low d oses increase slow wave sleep and reduce waking, whereas large doses increa se waking and reduce slow wave sleep and REM sleep. Direct injection of 8-O HDPAT or flesinoxan, another 5-HT1A agonist into the DRN, or microdialysis perfusion of 8-OHDPAT into the DRN significantly increases REMS. On the oth er hand, infusion of 8-OHDPAT into the LDT selectively inhibits REMS, as do es direct administration into the DRN of the 5-HT1A receptor antagonists pi ndolol or WAY 100635. Thus, presently available evidence indicates that sel ective activation of the somatodendritic 5-HT1A receptor in the DRN induces an increase of REMS. On the other hand, activation of the postsynaptic 5-H T1A receptor at the level of the PPT/LDT nuclei decreases REMS occurrence.