Diazepam and Ro 15-1788 increase absence epilepsy in WAG/Rij rats chronically exposed to diazepam.
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.
Peeters
B W
BW
Department of Comparative and Physiological Psychology, University of Nijmegen, The Netherlands.
Van Rijn
C M
CM
Nutt
D J
DJ
Titulaer
M N
MN
Vossen
J M
JM
Coenen
A M
AM
D000818:Animals; D003975:Diazepam / Q000494:pharmacology*; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D005442:Flumazenil / Q000494:pharmacology*; D006993:Hypnotics and Sedatives; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D006993:Hypnotics and Sedatives; D005442:Flumazenil; D003975:Diazepam