Effects of benzodiazepine receptor partial inverse agonists in the elevated plus maze test of anxiety in the rat.
The present series of experiments examined the effects of five benzodiazepine receptor (BZR) partial inverse agonists on the behaviour of rats on an elevated plus maze. The drugs were tested in a standard plus maze with 3-cm walls added to the open arms, as this has been shown to increase the sensitivity of the plus maze to anxiogenic-like drugs effects (Jones and Cole 1995). The drugs tested were FG 7142 (0-100 mg/kg), beta-CCE (0-30 mg/kg), ZK 132,556 (0-100 mg/kg), ZK 90 886 (0-30 mg/kg) and Ro 15-4513 (0-30 mg/kg). In addition, to allow a comparison with previous studies, the effects of three reference substances, DMCM (0-2.5 mg/kg), pentylenetetrazol (PTZ; 0-30 mg/kg) and yohimbine (0-5 mg/kg), were also examined. These three reference compounds produced a dose-dependent reduction in the duration of open arm exploration and the total number of open arm entries, indicative of anxiogenic-like effects. DMCM produced significant effects at the doses of 1.25 and 2.5 mg/kg, PTZ at 30 mg/kg, and yohimbine at 5 mg/kg. The BZR partial inverse agonist FG 7142 (10, 30 and 100 mg/kg) also reduced the duration of open arm exploration and the total number of arm entries. The minimally effective dose resulted in a receptor occupancy of approximately 80%. Ro 15-4513 also produced anxiogenic-like effects, but only at a dose (30 mg/kg) that resulted in a receptor occupancy of approximately 95%.(ABSTRACT TRUNCATED AT 250 WORDS)
Cole
B J
BJ
Department of Neuropsychopharmacology, Research Laboratories of Schering AG, Berlin, Germany.
Hillmann
M
M
Seidelmann
D
D
Klewer
M
M
Jones
G H
GH
D000818:Animals; D001007:Anxiety / Q000188:drug therapy*; D001067:Appetite Depressants / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D015016:Yohimbine / Q000494:pharmacology
D001067:Appetite Depressants; D002243:Carbolines; D003292:Convulsants; D058785:GABA-A Receptor Agonists; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D015016:Yohimbine; C035874:FG 7142