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• W1551796354 abstract "BACKGROUND AND PURPOSE Classic H 1 histamine receptor (H 1 R) antagonists are non‐selective for H 1 R and known to produce drowsiness. Modern antihistamines are more selective for H 1 R, and are ‘non‐drowsy’ presumably due to reduced permeability through the blood‐brain barrier. To characterize both histaminergic sleep regulation and the central actions of antihistamines, in the present study we analysed the effect of classic and modern antihistamines on rats' sleep using continuous i.c.v. infusions. EXPERIMENTAL APPROACH Effects of classic ( d ‐chlorpheniramine; d ‐CPA) and second‐generation (cetirizine) antihistamines on sleep were compared after i.p. injections or continuous i.c.v. infusions into rats. Fluorescent cetirizine/DBD‐pz was synthesized to trace the approximate distribution of cerebral cetirizine. Furthermore, the effects of H 1 R antagonists on cultured preoptic neurons were examined using calcium imaging. KEY RESULTS d ‐CPA 4 mg·kg −1 i.p. increased non‐rapid eye movement (REM) sleep whereas 10–40 mg·kg −1 d ‐CPA decreased non‐REM sleep at dark onset time. Nocturnal i.c.v. infusions of d ‐CPA (10 µmol·100 µL −1 ·10 h −1 ) increased drowsiness but not non‐REM sleep, whereas the same i.c.v. infusions of cetirizine significantly increased non‐REM sleep, abolished REM sleep, and decreased wakefulness for more than 10 h. The medial preoptic area contained the greatest fluorescent labelling after i.c.v. cetirizine/DBD‐pz infusions. Histamine‐induced Ca 2+ increases in medial preoptic neurons were blocked by d ‐CPA or cetirizine, whereas d ‐CPA, but not cetirizine, increased Ca 2+ irrespective of antihistaminergic activity at ≥100 µM. CONCLUSION AND IMPLICATIONS The excitatory action of d ‐CPA may explain the seemingly inconsistent actions of d ‐CPA on sleep. Cerebral H 1 R inhibition by cetirizine induces synchronization of cerebral activity and prolonged, continuous slow‐wave sleep." @default.
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• W1551796354 date "2011-12-06" @default.
• W1551796354 modified "2023-10-17" @default.
• W1551796354 title "Induction of prolonged, continuous slow-wave sleep by blocking cerebral H1 histamine receptors in rats" @default.
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• W1551796354 doi "https://doi.org/10.1111/j.1476-5381.2011.01547.x" @default.
• W1551796354 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3252975" @default.
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