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

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.