SEROTONIN AT THE LATERODORSAL TEGMENTAL NUCLEUS SUPPRESSES RAPID-EYE-MOVEMENT SLEEP IN FREELY BEHAVING RATS

Serotonin [5-hydroxytryptamine (5-HT)] is believed to play an importan t inhibitory role in the regulation of rapid-eye-movement (REM) sleep. 5-HT may exert this effect on neurons of the laterodorsal tegmental ( LDT) nuclei that are implicated as important in the generation of REM sleep and phasic REM events such as ponto-geniculo-occipital (PGO) wav es and respiratory variability. In rat brainstem in vitro, 5-HT hyperp olarizes and inhibits the bursting properties of LDT neurons assumed t o be involved in generating REM sleep and PGO waves. This study tests the hypothesis that in vivo 5-HT at the LDT nuclei suppresses REM slee p and phasic REM events. Ten rats were implanted with bilateral cannul ae aimed at the LDT and with electrodes for recording the electroencep halogram, neck electromyogram, PGO waves, and diaphragm electromyogram . During REM sleep, 5-HT (100 nl; 1-1.5 mM), saline, or sham microinje ctions were performed; repeated microinjections were separated by simi lar to 1 hr. After the first microinjection, REM sleep as a percent of the total sleep time was reduced with 5-HT (mean percent REM, 19.9 +/ - 2.5% for 5-HT vs 26.8 +/- 2.4% for saline; p = 0.02). REM duration w as reduced by 37% with 5-HT (p = 0.01), but REM episode frequency was changed less consistently (p = 0.21), suggesting that 5-HT mainly disr upted REM sleep maintenance. Per unit time of REM sleep, 5-HT had no e ffect on the amount or variability of REM PGO activity (p > 0.740) or on the mean or coefficient of variation of REM respiratory rate (p > 0 .11). With subsequent microinjections, the effects of 5-HT on REM slee p were similar. A dose-dependent REM sleep suppression with 5-HT was o bserved in five rats tested. These data suggest that in vivo 5-HT at t he LDT nuclei suppresses REM sleep expression. Although 5-HT did not d isproportionately reduce the occurrence of phasic events within REM, t otal REM phasic activity was reduced because of less REM sleep after 5 -HT.