Classical and novel approaches to the preclinical testing of anxiolytics: A critical evaluation

Over 80% of current anxiety studies employ one of the tests that were developed earlier than, or concurrently with the elevated plus-maze, i.e. before 1985. Considering 1985 as a historical reference point, we briefly review here 115 new tests and models of anxiety, the development of which was likely prompted by the poor predictive validity of classical tests as shown here by the comparison of preclinical and clinical findings with putative novel anxiolytics. The new approaches comprise major innovations to classical tests, the pre-test application of manipulations that mimic etiological factors of anxiety disorders, and entirely new approaches including anxiety disorder-specific tests. Thus, intensive test development over the last 27 years created a large pool of novel approaches. However, these are infrequently used and as such, their impact on anxiolytic drug development remains low. We suggest here that test/model development should step over the intensive phase when several new methods are proposed each year and should start selecting and establishing the methodologies that would successfully replace or complement classical tests. We propose here a novel strategy for improving the validity of anxiety testing that includes the retrospective analysis of the predictive validity of new procedures (as opposed to classical pharmacological validation), and a call for concerted international efforts at both the conceptual and practical levels. Similar endeavors proved recently successful with other psychiatric disorders.