A MODEL OF ANTIPREDATOR DEFENSE IN SWISS-WEBSTER MICE - EFFECTS OF BENZODIAZEPINE RECEPTOR LIGANDS WITH DIFFERENT INTRINSIC ACTIVITIES

A mouse defense test battery (MDTB) has been designed to assess defens ive reactions of Swiss-Webster mire to situations associated with nonp ainful threat. When compared to mice approached by a leather glove, an imals confronted with an anesthetized or a conscious rat displayed pot entiated flight responses and defensive threat/attack reactions, while risk assessment performances were generally similar in all three cond itions. Furthermore, escape attempt responses following removal of the stimulus were higher in the conscious rat condition compared to the t wo other groups. Taken together, these results suggest that flight rea ctions and defensive threat/attack responses are specific to the rat, and thus indicate that the MDTB may relate to 'antipredator' defense. In mice confronted with an anaesthetized rat, administration of the be nzodiazepine (BZ) receptor full agonist chlordiazepoxide (5-25 mg/kg, i.p., 30 min) and the BZ partial agonist Ro 19-8022 (0.5-2 mg/kg, i.p. , 30 min) altered one of two risk assessment measures and inhibited de fensive attack behaviors, but failed to counter the post-predator incr ease in escape attempts. In addition, Ro 19-8022 also strongly reduced flight responses. The overall behavioral profile suggests a fear/anxi ety-reducing action of both drugs. By contrast, administration of the BZ inverse agonist Ro 19-4603 (0.025-0.1 mg/kg, i.p., 30 min) reliably released these defensive responses. Interestingly, the BZ antagonist flumazenil (5-20 mg/kg, i.p., 30 min) manifested differential intrinsi c activity depending upon the level of threat. Thus, in a weakly threa tening situation, the drug potentiated flight reactions, indicating an inverse agonist-like action, decreased defensive biting in a highly t hreatening situation, indicating an agonist activity. These findings d emonstrated that BZ ligands differently modulated 'antipredator' defen se in Swiss-Webster mice, depending upon their intrinsic (positive or negative) efficacy, but also depending upon the defense strategy requi red by the threat.