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 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.