Animal models of anxiety and anxiolytic drug action

Animal models of anxiety attempt to represent some aspect of the etiology, symptomatology, or treatment of human anxiety disorders, in order to facilitate their scientific study. Within this context, animal models of anxiolytic drug action can be viewed as treatment models relevant to the pharmacological control of human anxiety. A major purpose of these models is to identify novel anxiolytic compounds and to study the mechanisms whereby these compounds produce their anxiolytic effects. After a critical analysis of "face," "construct," and "predictive" validity, the biological context in which animal models of anxiety are to be evaluated is specified. We then review the models in terms of their general pharmacological profiles, with particular attention to their sensitivity to 5-HT1A agonists and antidepressant compounds. Although there are important exceptions, most of these models are sensitive to one or perhaps two classes of anxiolytic compounds, limiting their pharmacological generality somewhat, but allowing in depth analysis of individual mechanisms of anxiolytic drug action (e.g., GABA_A agonism). We end with a discussion of possible sources of variability between models in response to 5-HT1A agonists and antidepressant drugs.