By contrast, pathological anxiety is an inappropriate response to an external or internal stimulus. In light of the high complexity of anxiety disorders and the comorbidity with MDD, the selleck screening library chance of succeeding in developing comprehensive animal models that accurately reflect the relative influences of contributing factors in humans is probably quite poor.39 However, as outlined below, ample opportunity exists to better define and extend existing models and to develop new experimental setups that consider the impact of combined factors in determining anxious behavior. The examples summarized in this part of the Inhibitors,research,lifescience,medical article have been selected because they model

cardinal symptoms of anxiety but not depressive disorders. Validity criteria for animal models of anxiety disorders Numerous procedures with experimental animals have been developed to facilitate preclinical

research on the behavioral pharmacology of anxiety and, as a result Inhibitors,research,lifescience,medical of this aim, are often referred to as “animal models of anxiety.” This is an unfortunate error in terminology, not only because it implies that anxiety is a unitary emotional state, but also because of the apparent inability Inhibitors,research,lifescience,medical of many tests to consistently detect the anxiolytic effects of novel drugs.40 The discovery of benzodiazepines (BZs) about 50 years ago, and their therapeutic and commercial success in the treatment of anxiety, has stimulated the development Inhibitors,research,lifescience,medical of a number of experimental test procedures. Because BZs were the only effective anxiolytic drugs at that time, the predictive validity of the animal models has been mainly based on their ability to detect the pharmacological action of BZs and related compounds. Later, clinicians discovered that patients can become addicted to BZ, and consequently paid more attention to non-benzodiazepine anxiolytics. However, it turned out that these new drugs were a challenge to the validity of the existing screening models. The best known example is Inhibitors,research,lifescience,medical buspirone, a clinically effective serotonin (5-HT)1A receptor partial agonist

whose anxiolytic potential was missed by conventional screening procedures in animals, in particular conflict tests in rats, and was only recognized during clinical assessments for possible antipsychotic efficacy.41 This was the time when unconditioned conflict tests such as the elevated plus-maze were developed.42 A further complication appeared when it became evident that anxiety is not a unitary phenomenon, but could be divided into TCL various forms including “normal” or “state” anxiety on the one hand and “pathological” or “trait” anxiety on the other hand. According to today’s terminology, pathological anxiety should not be considered just as an excess of normal anxiety, but it rather appears that the pathological forms have a different neurobiological basis. Furthermore, the various forms of human anxiety disorders have been shown to be differentially sensitive to pharmacological treatment.