Dopaminergic Modulation of Behavioral States in Mesopontine Tegmentum: A Reverse Microdialysis Study in Freely Moving Cats

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Abstract
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. 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. NA NA NA 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 α, a region located just ventromedial to the locus coeruleus, pars α, 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 SKF81297, 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 slowwave sleep and PS. The effects of DA were mimicked, however, by application of clonidine, a selective α2 adrenoceptor agonist, and blocked by co-application of RX821002, a selective antagonist of α2 adrenoceptors. Our results indicate that DA inhibits PS in the peri-locus coeruleus α via excitation of α2 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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