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 p redator, a rat. These behaviors include flight, avoidance, defensive t hreat/attack responses, and risk assessment activities. Previous studi es with the MDTB have suggested that this model may have some utility for the investigation of panicogenic and antipanic compounds. In the p resent 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. inje ction during 10 days) treatment with the benzodiazepine receptor (BZPR ) full agonist and panicolytic agent alprazolam. At non motor-impairin g doses (0.05-0.5 mg/kg), acute alprazolam failed to alter the avoidan ce distance between the subject and the predator, the number of avoida nces when the rat is approaching, predator assessment activities, defe nsive threat/attack responses when contact is forced between the subje ct and the predator or contextual escape attempts after the predator w as removed. This was in contrast to chronic treatment which decreased both avoidance variables at 0.5 and 1 mg/kg, defensive threat/attack r esponses 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 find ings with the BZPR full agonist chlordiazepoxide, indicating that thes e compounds generally attenuate antipredator defensive responses in Sw iss-Webster mice; (2) support recent data indicating that panic-alteri ng drugs modulate flight/escape reactions, and suggest that the primar y mechanism of action of drugs with efficacy against panic disorder ma y involve neural systems controlling flight; (3) confirm that the MDTB may be useful for the investigation of panicolytic as well as anxioly tic agents.