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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Involvement of the "peripheral" benzodiazepine receptor type (omega 3) in the tolerance to the electroencephalographic effects of benzodiazepines in rats: comparison of diazepam and clonazepam.

Rapid tolerance to the sedative effect of large doses of diazepam (10 mg/kg IV), but not of large doses of clonazepam (2 mg/kg IV) occurs in rats after 5 days of treatment on a once-a-day regimen. Electroencephalographic (EEG) studies show that such behavioral tolerance is associated with a decreased induction of spindle bursts and with an increased induction of 20-30 Hz waves (beta-like activity). Administration of clonazepam plus the agonist of the "peripheral" benzodiazepine receptor type (omega 3) Ro 5-4864 (4 mg/kg IV) for 5 days induces signs of behavioral and EEG tolerance to sedative effects of the benzodiazepine agonist. In animals treated for 5 days with diazepam plus the omega 3 antagonist PK 11195 (5 mg/kg IV), no signs of EEG and behavioral tolerance are observed. These results suggest that omega 3 type activation influences the development of rapid tolerance to the sedative effect of diazepam in rats.[1]


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