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  • Title: Dopaminergic modulation of behavioral states in mesopontine tegmentum: a reverse microdialysis study in freely moving cats.
    Author: Crochet S, Sakai K.
    Journal: Sleep; 2003 Nov 01; 26(7):801-6. PubMed ID: 14655911.
    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.
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