Behavioral neurobiology of inverse agonist FG 7142 induced anxiety syndrome in rats. 1990

R Shanbhogue, and H J Hrishikeshavan, and K Devi, and S Munonyedi
Department of Pharmacology, Kasturba Medical College, Manipal, India.

1. Neurobehavioral survey of inverse agonist FG 7142 was performed employing a novel anxiety paradigm namely FR-2 Two-Way crossover in a shuttle box. 2. FG syndrome was found to be similar to learned helplessness following shock treatment. Significant increase in mean latency to escape was observed from 0 to 25th trial. Effect of FG 7142 on the behavioral and neurological profile did not deviate significantly from controls. However, a general increase in arousal, darting and sideway movement (weaving) of the head were noted. 3. Drugs with specificity at benzodiazepine (BDZ) receptor site were employed as pretreatments in order to study their influence on FG 7142 induced anxiety syndrome. Diazepam and ZK 91296, significantly blocked the inverse agonist response. Head weaving as well as darting movements were completely abolished although rats demonstrated arousal and vigilance. 4. A dose dependent inhibition of FG response was observed with RO 15-1788, a specific BDZ receptor blocker. ZK 93423 at low doses (1 mg/kg) failed to reverse the escape deficit induced by FG. Higher doses of ZK 93423 could not be tested as significant sedation and ataxia were noted. 5. It is suggested that a careful combination of a BDZ agonist and inverse agonist may be beneficial in the treatment of generalised anxiety disorders.

UI MeSH Term Description Entries
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D002243 Carbolines A group of pyrido-indole compounds. Included are any points of fusion of pyridine with the five-membered ring of indole and any derivatives of these compounds. These are similar to CARBAZOLES which are benzo-indoles. Carboline,Pyrido(4,3-b)Indole,Beta-Carbolines,Pyrido(4,3-b)Indoles,Beta Carbolines
D003975 Diazepam A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity. 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,Apaurin,Diazemuls,Faustan,Relanium,Seduxen,Sibazon,Stesolid,Valium
D005106 Exploratory Behavior The tendency to explore or investigate a novel environment. It is considered a motivation not clearly distinguishable from curiosity. Curiosity,Novelty-Seeking Behavior,Behavior, Exploratory,Behavior, Novelty-Seeking,Behaviors, Exploratory,Behaviors, Novelty-Seeking,Curiosities,Exploratory Behaviors,Novelty Seeking Behavior,Novelty-Seeking Behaviors
D005442 Flumazenil A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses. Flumazepil,Anexate,Lanexat,Ro 15-1788,Romazicon,Ro 15 1788,Ro 151788
D006120 Grooming An animal's cleaning and caring for the body surface. This includes preening, the cleaning and oiling of feathers with the bill or of hair with the tongue. Preening,Groomings,Preenings
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001008 Anxiety Disorders Persistent and disabling ANXIETY. Anxiety Neuroses,Anxiety States, Neurotic,Neuroses, Anxiety,Anxiety Disorder,Anxiety State, Neurotic,Disorder, Anxiety,Disorders, Anxiety,Neurotic Anxiety State,Neurotic Anxiety States,State, Neurotic Anxiety,States, Neurotic Anxiety

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