Central administration of two 5-HT receptor agonists: effect on REM sleep initiation and PGO waves

Cholinergic neurons in the pedunculopontine tegmental (PPT) and the laterodorsal tegmental (LDT) nuclei are implicated in the generation of rapid eye movement sleep (REM) and ponto-geniculo-occipital (PGO) waves. Serotonin (5-HT) has a role in sleep-wake regulation and appears to inhibit PGO wave generation. We studied the effects of the central infusion of the relatively specific 5-HT1A receptor agonist 8-hydroxy-2-(n-dipropylamino)tetralin (DPAT) and the less specific 5-HT1 receptor agonist 1(3-chlorophenyl)piperazine (mCPP) on the regulation of REM and on PGO wave generation. DPAT (0.0, 0.002, 0.01, 0.08, and 0.8 microgram/0.5 microliter normal saline) and mCPP (0.0, 0.02, 0.2, 2.0, and 20.0 micrograms/0.5 microliter normal saline) were infused unilaterally into the peribrachial region of PPT (PB) in cats. Additionally, DPAT (0.01 microgram/0.5 microliter) was infused bilaterally into PB in a separate experiment. Low dosages of DPAT (unilateral or bilateral) decreased successful entrances into REM (0.01 microgram) and time spent asleep (0.002 microgram and 0.01 microgram) without affecting outward behavior. No dosage of mCPP significantly decreased the number of REM episodes, and neither drug decreased REM episode duration once REM had been entered. Neither drug affected the rate of PGO waves independently of modulating behavioral state. We propose that 5-HT1A receptor mechanisms have an inhibitory role in actual REM initiation, possibly by facilitating endogenously generated excitation of brainstem startle mechanisms at the onset of REM.