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

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 D-1-like agonist, or selective D-2-like agonists such as quinelorane, quinpirole, and 7-OH-DPAT. Instead, D-2-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 alpha(2) adrenoceptor agonist, and blocked by co-application of RX821002, a selective antagonist Of alpha(2) adrenoceptors. Conclusions: Our results indicate that DA inhibits PS in the peri-locus coeruleus alpha via excitation Of alpha(2) adrenoceptors, but application of D-2-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.