Dopaminergic modulation of behavioral states in mesopontine tegmentum: a reverse microdialysis study in freely moving cats. 2003

Sylvain Crochet, and Kazuya Sakai
INSERM U480, IFR 19, Université Claude Bernard Lyon I, Lyon, France. crochet@univ-lyon1.fr

OBJECTIVE 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. METHODS 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. METHODS NA. METHODS NA. METHODS NA. 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.

UI MeSH Term Description Entries
D008124 Locomotion Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. Locomotor Activity,Activities, Locomotor,Activity, Locomotor,Locomotor Activities
D008297 Male Males
D011149 Pons The front part of the hindbrain (RHOMBENCEPHALON) that lies between the MEDULLA and the midbrain (MESENCEPHALON) ventral to the cerebellum. It is composed of two parts, the dorsal and the ventral. The pons serves as a relay station for neural pathways between the CEREBELLUM to the CEREBRUM. Pons Varolii,Ponte,Pons Varolius,Pontes,Varolii, Pons,Varolius, Pons
D002415 Cats The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801) Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004569 Electroencephalography Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. EEG,Electroencephalogram,Electroencephalograms
D004576 Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Electromyogram,Surface Electromyography,Electromyograms,Electromyographies,Electromyographies, Surface,Electromyography, Surface,Surface Electromyographies
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors

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