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

Abstract

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-HT 1A receptor agonist 8-hydroxy-2-(n-dipropylamino)tetralin (DPAT) and the less specific 5-HT 1 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 μg/0.5 μl normal saline) and mCPP (0.0, 0.02, 0.2, 2.0, and 20.0 μg/0.5 μl normal saline) were infused unilaterally into the peribrachial region of PPT (PB) in cats. Additionally, DPAT (0.01 μg/0.5 μl) was infused bilaterally into PB in a separate experiment. Low dosages of DPAT (unilateral or bilateral) decreased successful entrances into REM (0.01 μg) and time spent asleep (0.002 μg and 0.01 μg) 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-HT 1A 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.