title: Sodium phenobarbitone reverses the anxiogenic effects of compounds acting at three different central sites.
abstract: Sodium phenobarbitone was tested for its ability to antagonise the anxiogenic effects of compounds acting at three different central sites. These compounds were: FG 7142, a beta-carboline which acts at the benzodiazepine binding site on the GABA-benzodiazepine receptor complex; pentylenetetrazole, which acts at the picrotoxinin site on the GABA-benzodiazepine receptor complex; and yohimbine which is an antagonist at the alpha 2-adrenoceptor. The experiments were carried out in two tests of anxiety using rats. In the social interaction test (the test arena was familiar and dimly lit), FG 7142 (5 mg/kg) and pentylenetetrazole (15 mg/kg) reduced the time spent in social interaction (indicating anxiogenic activity); these effects were reversed by sodium phenobarbitone (35 mg/kg). Sodium phenobarbitone (35 mg/kg) alone decreased locomotor activity as measured in the social interaction test, which was reversed by pentylenetetrazole (15 mg/kg). In the elevated plus-maze, FG 7142 (6.7 mg/kg) pentylenetetrazole (20 mg/kg) and yohimbine (4 mg/kg) reduced the percentage of open-arm entries and the percentage of time spent on the open arms (indicating anxiogenic activity); these effects were reversed by sodium phenobarbitone (35 mg/kg). Sodium phenobarbitone (35 mg/kg) alone significantly increased the percentage of open-arm entries and the percentage of time spent on the open arms (indicating anxiolytic activity). This study, together with previous studies using other clinically-effective anxiolytic drugs, suggests that the ability of a compound to antagonise the effects of anxiogenic agents may be a useful indirect means of predicting anxiolytic activity.
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of London, U.K.
authors.forename: A L
authors.initials: AL
authors.lastname: Johnston
authors.forename: S E
authors.initials: SE
authors.lastname: File
mesh_terms: D000818:Animals; D001007:Anxiety; D001067:Appetite Depressants / Q000037:antagonists & inhibitors*; D002243:Carbolines / Q000037:antagonists & inhibitors*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects; D012919:Social Behavior; D015016:Yohimbine / Q000037:antagonists & inhibitors*
chemical_list: D001067:Appetite Depressants; D002243:Carbolines; D011942:Receptors, Adrenergic, alpha; D011963:Receptors, GABA-A; D015016:Yohimbine; C035874:FG 7142; D010433:Pentylenetetrazole; D010634:Phenobarbital