Further evidence that the Mouse Defense Test Battery is useful for screening anxiolytic and panicolytic drugs: Effects of acute and chronic treatment with alprazolam

The Mouse Defense Test Battery (MDTB) has been designed to investigate defensive responses of Swiss-Webster mice confronted with a natural predator, a rat. These behaviors include flight, avoidance, defensive threat/attack responses, and risk assessment activities. Previous studies with the MDTB have suggested that this model may have some utility for the investigation of panicogenic and antipanic compounds. In the present study the MDTB was used to investigate the effects of acute (0.05-1 mg/kg, i.p., 30 min) or chronic (0.5-2 mg/kg, one daily i.p. injection during 10 days) treatment with the benzodiazepine receptor (BZPR) full agonist and panicolytic agent alprazolam. At non motor-impairing doses (0.05-0.5 mg/kg), acute alprazolam failed to alter the avoidance distance between the subject and the predator, the number of avoidances when the rat is approaching, predator assessment activities, defensive threat/attack responses when contact is forced between the subject and the predator or contextual escape attempts after the predator was removed. This was in contrast to chronic treatment which decreased both avoidance variables at 0.5 and 1 mg/kg, defensive threat/attack responses at all doses, and predator assessment responses at 0.5 mg/kg. In addition, the latter treatment reduced post-predator potentiation of escape attempts at 2 mg/kg. These results (1) confirm previous findings with the BZPR full agonist chlordiazepoxide, indicating that these compounds generally attenuate antipredator defensive responses in Swiss-Webster mice; (2) support recent data indicating that panic-altering drugs modulate flight/escape reactions, and suggest that the primary mechanism of action of drugs with efficacy against panic disorder may involve neural systems controlling flight; (3) confirm that the MDTB may be useful for the investigation of panicolytic as well as anxiolytic agents.