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Sleep. 2003 Nov 1;26(7):801-6.

Dopaminergic modulation of behavioral states in mesopontine tegmentum: a reverse microdialysis study in freely moving cats.

Author information

  • 1INSERM U480, IFR 19, Universit√© Claude Bernard Lyon I, Lyon, France. crochet@univ-lyon1.fr

Abstract

STUDY OBJECTIVES:

We investigated the role of dopamine (DA) in behavioral state control and, in particular, paradoxical (or rapid eye movement) sleep (PS) generation in mesopontine structures.

DESIGN:

Reverse microdialysis and polygraphic recordings in freely moving cats were used to assess the effects on sleep-wake states of applied DA and monoaminergic agonists and antagonists.

SETTINGS:

NA.

PATIENTS OR PARTICIPANTS:

NA.

INTERVENTION:

NA.

MEASUREMENTS AND RESULTS:

Quantitative and qualitative analysis of behavioral states and electroencephalogram showed that DA had no significant effect when applied to any part of the mesopontine tegmentum, except the peri-locus coeruleus alpha, a region located just ventromedial to the locus coeruleus, pars alpha, and critically implicated in PS generation. In this structure, DA caused a selective and dose-dependent inhibition of PS and induced PS without atonia. These effects were not mimicked by SKF-81297, a selective D1-like agonist, or selective D2-like agonists such as quinelorane, quinpirole, and 7-OH-DPAT. Instead, D2-like agonists induced a significant decrease in wakefulness and increases in both slow-wave sleep and PS. The effects of DA were mimicked, however, by application of clonidine, a selective alpha2 adrenoceptor agonist, and blocked by co-application of RX821002, a selective antagonist of alpha2 adrenoceptors.

CONCLUSIONS:

Our results indicate that DA inhibits PS in the peri-locus coeruleus alpha via excitation of alpha2 adrenoceptors, but application of D2-like agonists to the same region markedly decreases wakefulness and increases both slow-wave sleep and PS. This effect may be responsible for the excessive daytime sleepiness and sleep attacks induced by antiparkinsonian dopaminergic agents.

PMID:
14655911
[PubMed - indexed for MEDLINE]
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