In vivo microdialysis measures of extracellular serotonin in the rat hippocampus during sleep–wakefulness

doi:10.1016/S0006-8993(99)01511-5

Brain Research

Volume 833, Issue 2, 3 July 1999, Pages 291-296

https://doi.org/10.1016/S0006-8993(99)01511-5 Get rights and content

Abstract

We investigated extracellular 5-hydroxytryptamine (5-HT) levels in rat hippocampus during different stages of the sleep–waking cycle using in vivo microdialysis. The extracellular 5-HT level was highest in active waking (AW) and, when compared to AW, 5-HT level was progressively lower in quiet waking (QW; 78%), quiet sleep (QS; 50%) and REM (which we termed active sleep (AS); 40%). Functional implications of AS related-decreased 5-HT in the hippocampus are discussed.

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Acknowledgements

We wish to thank Joyel Almajano for technical assistance, Toan Do and Larry Ackerson for HPLC analysis, and Tony Fields for EEG recording assistance. Faustino Lopez-Rodriguez was supported by a Program in Minority Research Training in Psychiatry Fellowship, funded by NIMH, MH 19126. Funding was provided by NIH grants NS 33310 and NS 02808.

References (24)

B. Bjorvatn et al.
Sleep/waking effects of a selective 5-HT1A receptor agonist given systemically as well as perfused in the dorsal raphe nucleus in rats
Brain Research
(1997)
M.-C. Buhot
Serotonin receptors in cognitive behaviors
Current Opinion in Neurobiology
(1997)
R. Cespuglio et al.
Single unit recording in the nuclei raphe dorsalis and magnus during the sleep–waking cycle of semi-chronic prepared cats
Neuroscience Letters
(1981)
C. Fornal et al.
Activity of serotonin-containing neurons in nucleus raphe magnus in freely moving cats
Experimental Neurology
(1985)
H. Iwakiri et al.
Extracellular levels of serotonin in the medial pontine reticular formation in relation to sleep–wake cycle in cats: a microdialysis study
Neuroscience Research
(1993)
F. Marrosu et al.
Microdialysis measurement of cortical and hippocampal acetylcholine release during sleep–wake cycle in freely moving cats
Brain Research
(1995)
D.J. McGinty et al.
Dorsal raphe neurons: depression of firing during sleep in cats
Brain Research
(1976)
C.M. Portas et al.
On-line detection of extracellular levels of serotonin in dorsal raphe nucleus and frontal cortex over the sleep/wake cycle in the freely moving rat
Neuroscience
(1998)
C.M. Portas et al.
Behavioral state-related changes of extracellular serotonin concentration in the dorsal raphe nucleus: a microdialysis study in the freely moving cat
Brain Research
(1994)
K. Rasmussen et al.
Activity of serotonin-containing neurons in nucleus centralis superior of freely moving cats
Experimental Neurology
(1984)

L.E. Rueter et al.

A microdialysis examination of serotonin release in the rat forebrain induced by behavioral/environmental manipulations

Brain Research

(1996)

K. Shima et al.

Firing properties of two types of nucleus raphe dorsalis neurons during the sleep–waking cycle and their responses to sensory stimuli

Brain Research

(1986)

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Short communicationIn vivo microdialysis measures of extracellular serotonin in the rat hippocampus during sleep–wakefulness

Abstract

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Acknowledgements

Brain Research

Current Opinion in Neurobiology

Neuroscience Letters

Experimental Neurology

Neuroscience Research

Brain Research

Brain Research

Neuroscience

Brain Research

Experimental Neurology

Brain Research

Brain Research

Short communication
In vivo microdialysis measures of extracellular serotonin in the rat hippocampus during sleep–wakefulness