Effects of activation and blockade of 5-HT2A/2C receptors in the dorsal raphe nucleus on sleep and waking in the rat.

The effects of the 5-HT(2A/2C) receptor agonist DOI and of the selective 5-HT(2A) or 5-HT(2C) receptor antagonists EMD 281014 and SB-243213, respectively, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. The serotonergic ligands were microinjected directly into the dorsal raphe nucleus (DRN). Infusion of DOI (1.4-5.6 mmol) into the DRN induced a significant reduction of REM sleep (REMS) and of the number of REM periods. Following the microinjection of EMD 281014 (5.6 mmol) or SB-243213 (1.4-2.8 mmol) light sleep (LS) was slightly but significantly augmented. Pretreatment with EMD 281014 or SB-243213 antagonized the DOI-induced decrease of REMS. It is proposed that suppression of REMS after DOI microinjection into the DRN is related to the activation of GABAergic projection neurons that synapse cholinergic neurons in the laterodorsal and peduncunculopontine tegmental nuclei (LDT/PPT) involved in the promotion of REMS.