Schizophrenia presents with positive/psychotic, negative and
cognitive symptoms. Positive symptoms seems due to a
dopamine mesolimbic overreactivity, while negative/
cognitive symptoms may conversely be due to mesocortical hypo-dopaminergia. Traditional
dopamine D2 receptor blocking
antipsychotics (e.g.
haloperidol) are effective against psychotic/positive symptoms, but less so against negative/
cognitive symptoms. Some D2 receptor blockage, however, seems necessary for efficacy against psychotic symptoms. Therefore, current
antipsychotic drug improvement strategies include modest D2 receptor blockage, or partial D2 stimulation, combined with adjunct pharmacological properties that may enhance: i) D2 blockage efficacy; and ii) cognitive functioning. There are also strategies with no direct D2 blockage. Clinical activity is often tested in animal screening tests (so called animal models). The screening test conditioned avoidance response in rats has shown particular sensitivity, with high predictive validity, for detection of
drug antipsychotic activity. The present review assessed the significance, accuracy and use of the conditioned avoidance response test as a screening tool in current
antipsychotic drug development. It was found that: i) the conditioned avoidance response test holds a strong position, is frequently used in current
antipsychotic drug development, and is commonly considered a reliable screening tool, with high predictive validity, for the detection of potential
antipsychotic activity; ii) in current
antipsychotic drug development, the conditioned avoidance response test is able to detect pharmacological properties contributing to
antipsychotic activity in the presence of sub-therapeutic D2 receptor blockade, as well as detecting
antipsychotic activity of compounds having no direct D2 blocking properties.