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 important 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) waves and respiratory variability. In rat brainstem in vitro, 5-HT hyperpolarizes and inhibits the bursting properties of LDT neurons assumed to 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 sleep and phasic REM events. Ten rats were implanted with bilateral cannulae aimed at the LDT and with electrodes for recording the electroencephalogram, neck electromyogram, PGO waves, and diaphragm electromyogram. During REM sleep, 5-HT (100 nl; 1-1.5 mM), saline, or sham microinjections were performed; repeated microinjections were separated by approximately 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 was 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 disrupted REM sleep maintenance. Per unit time of REM sleep, 5-HT had no effect 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 sleep were similar. A dose-dependent REM sleep suppression with 5-HT was observed in five rats tested. These data suggest that in vivo 5-HT at the LDT nuclei suppresses REM sleep expression. Although 5-HT did not disproportionately reduce the occurrence of phasic events within REM, total REM phasic activity was reduced because of less REM sleep after 5-HT.