Defense system psychopharmacology: an ethological approach to the pharmacology of fear and anxiety.

Defensive behaviors comprise a set of flexible and adaptive responses to threatening situations and stimuli. In semi-natural situations affording a wide variety of responses, defensive behaviors change over time in response to information about the presence of danger, acquired through risk assessment activities. Two test batteries, a Fear/Defense Test Battery (F/DTB) measuring defensive behaviors to present, approaching predators, and an Anxiety/Defense Test Battery (A/DTB) measuring reactions to potential threat, have been used in conjunction with administration of potentially anxiolytic drugs. Results suggest that the F/DTB behaviors are not systematically responsive to anxiolytics. However, on the A/DTB, anxiolytic benzodiazepines produce a profile of effects primarily involving risk assessment activities. Very similar profiles of effect are seen also with some 5-HT1A compounds, alcohol, imipramine and MK-801, but not for a variety of additional compounds. A consistent pattern of gender differences are obtained with the A/DTB, with females more defensive than males. These results indicate that particular patterns of defensive behaviors may provide a very appropriate animal model for the analysis of pharmacological effects on anxiety.