MICRODIALYSIS PERFUSION OF 8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN (8-OH-DPAT) IN THE DORSAL RAPHE NUCLEUS DECREASES SEROTONIN RELEASE AND INCREASES RAPID EYE-MOVEMENT SLEEP IN THE FREELY MOVING CAT

In vivo microdialysis was used to analyze the role of dorsal raphe nuc leus (DRN) neurons in regulating the sleep-waking cycle. Measurements of extracellular serotonin (5-HT) were made in the DRN of freely movin g adult cats before and during microdialysis perfusion of 8-hydroxy-2- (di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A receptor ag onist, in artificial CSF. Behavioral state alterations were measured b y simultaneous polygraphic recordings. During waking and artificial CS F perfusion of probes histologically localized to the DRN, extracellul ar 5-HT was 4 fmo1/7.5 mu l dialysate sample. With the addition of 8-O H-DPAT (10 mu M in artificial CSF) to the perfusate, 5-HT levels in th e same state decreased 50%, to 2 fmol/sample (p < 0.01), presumably th rough 5-HT1A autoreceptor-mediated inhibition of serotonergic neural a ctivity. Concomitantly, this 8-OH-DPAT perfusion produced a short late ncy, threefold increase in rapid eye movement (REM) sleep, from 10 to 30% of the total recorded time (p < 0.05), whereas waking was not sign ificantly affected. In contrast, and suggesting DRN specificity, 8-OH- DPAT delivery through a probe in the aqueduct did not increase REM sle ep but rather tended to increase waking and decrease slow wave sleep. The data on REM sleep provide the first biochemically validated and di rect evidence that suppression of DRN serotonergic activity increases REM sleep, and furnish a key complement to our laboratory's in vitro d ata indicating that mesopontine cholinergic neurons, a target of DRN p rojections, are inhibited by 5-HT. The 8-OH-DPAT-induced reduction of DRN 5-HT is consistent with the hypothesis that the concomitant REM sl eep disinhibition is mediated by DRN serotonergic projections to mesop ontine cholinergic neurons, which other data implicate in REM sleep pr oduction.