Diazepam and Ro 15-1788 increase absence epilepsy in WAG/Rij rats chronically exposed to diazepam

European Journal of Pharmacology
B W PeetersA M Coenen

Abstract

The mechanisms underlying tolerance to benzodiazepines were investigated by injecting diazepam (5 mg/kg) twice daily for 23 days in WAG/Rij rats (an animal model for non-convulsive absence epilepsy). After this the rats received either the agonist, diazepam, or the antagonist, flumazenil (Ro 15-1788). EEG analyses showed that both compounds increased the amount of absence epilepsy-like phenomena. This suggests that repeated administration of diazepam moves the benzodiazepine receptor spectrum towards the inverse agonist end.

References

Jan 1, 1989·Pharmacology, Biochemistry, and Behavior·A M Coenen, E L van Luijtelaar
Oct 1, 1988·Trends in Pharmacological Sciences·J R Haigh, M Feely
Oct 20, 1986·Neuroscience Letters·E L van Luijtelaar, A M Coenen
Feb 18, 1986·European Journal of Pharmacology·S F Gonsalves, D W Gallager
Apr 9, 1981·Nature·W HunkelerW Haefely

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