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Journal of Neuroscience, Vol 16, 2820-2828, Copyright © 1996 by Society for Neuroscience
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
CM Portas, M Thakkar, D Rainnie and RW McCarley
Department of Psychiatry, Harvard Medical School and Brockton VA Medical Center, Brockton, Massachusetts 02401, USA.
In vivo microdialysis was used to analyze the role of dorsal raphe nucleus
(DRN) neurons in regulating the sleep-waking cycle. Measurements of
extracellular serotonin (5-HT) were made in the DRN of freely moving adult
cats before and during microdialysis perfusion of 8-
hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A
receptor agonist, in artificial CSF. Behavioral state alterations were
measured by simultaneous polygraphic recordings. During waking and
artificial CSF perfusion of probes histologically localized to the DRN,
extracellular 5-HT was 4 fmol/7.5 micro L dialysate sample. With the
addition of 8-OH-DPAT (10 microM in artificial CSF) to the perfusate, 5- HT
levels in the same state decreased 50%, to 2 fmol/sample (p < 0.01),
presumably through 5-HT1A autoreceptor-mediated inhibition of serotonergic
neural activity. Concomitantly, this 8-OH-DPAT perfusion produced a short
latency, threefold increase in rapid eye movement (REM) sleep, from 10 to
30% of the total recorded time (p < 0.05), whereas waking was not
significantly affected. In contrast, and suggesting DRN specificity,
8-OH-DPAT delivery through a probe in the aqueduct did not increase REM
sleep but rather tended to increase waking and decrease slow wave sleep.
The data on REM sleep provide the first biochemically validated and direct
evidence that suppression of DRN serotonergic activity increases REM sleep,
and furnish a key complement to our laboratory's in vitro data indicating
that mesopontine cholinergic neurons, a target of DRN projections, are
inhibited by 5-HT. The 8-OH-DPAT-induced reduction of DRN 5-HT is
consistent with the hypothesis that the concomitant REM sleep disinhibition
is mediated by DRN serotonergic projections to mesopontine cholinergic
neurons, which other data implicate in REM sleep production.
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