The pentylenetetrazole-cue antagonist actions of bretazenil (Ro 16-6028) as compared to midazolam.
In order to compare the potencies of bretazenil (Ro 16-6028) and midazolam (MDZ) to antagonize the pentylenetetrazole (PTZ) cue, rats were trained to discriminate between 15 mg/kg IP PTZ and saline (FR10, food reinforced). Additionally, other rats were trained to discriminate between 1.0 mg/kg IP MDZ and saline in order to investigate the degree of generalization of bretazenil to MDZ, and to test for the antagonizing effects of PTZ. Both bretazenil and MDZ were able to block the PTZ cue. Bretazenil was about 60 times more potent than MDZ in this respect. In tests for response generalization, bretazenil substituted for MDZ cue. Bretazenil did not show MDZ-antagonist actions. PTZ did block the MDZ cue and the generalization of bretazenil in the MDZ-trained animals. Assuming that the drug discriminative stimulus functions of PTZ are closely related to its anxiogenic effects, it was concluded that bretazenil may possess powerful anxiolytic properties. Bretazenil did not suppress the response rates which is consistent with previous studies reporting a lack of sedative and muscle-relaxant effects of bretazenil.
Department of Psychopharmacology, Faculty of Pharmacy, University of Utrecht, The Netherlands.
H J
HJ
Rijnders
T U
TU
Järbe
J L
JL
Slangen
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D003463:Cues; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005793:Generalization, Psychological / Q000187:drug effects; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains
D001570:Benzodiazepinones; C054626:bretazenil; D008874:Midazolam; D010433:Pentylenetetrazole