Stressor controllability, social interaction, and benzodiazepine systems.

Effects of benzodiazepine receptor-active compounds on inescapable shock-produced changes in social interaction were studied in the rat. Inescapably shocked animals exhibited less social interaction in a novel situation than did escapably shocked or unshocked rats 24 h after shock. Administration of the selective benzodiazepine receptor antagonist flumazenil at the time of shock prevented the decrease in social interaction. Social interaction was unaffected by the same treatment at the time of measurement. Reduction in social interaction induced by inescapable stress endured for 48-72 h following stressor exposure but was absent 168 h after stress. It was subject to antagonist blockade at all measured time points. Stress-induced decreases in social interaction were also blocked by the benzodiazepine chlordiazepoxide given at the time of shock treatment. The receptor antagonist did not reverse this blockade. An inverse agonist, the beta-carboline FG 7142, administered in place of inescapable shock, produced an identical pattern of social interaction in a dose-dependent manner. The inverse agonist effect was also reversed by the antagonist. The results from antagonist, agonist, and inverse agonist treatments all suggest that an endogenous benzodiazepine receptor inverse agonist is released at the time of inescapable shock and is involved in producing the changes in social interaction subsequently measured.