Consideration of species differences in developing novel molecules as cognition enhancers

The NIH-funded CNTRICS initiative has coordinated efforts to promote the vertical translation of novel procognitive molecules from testing in mice, rats and non-human primates, to clinical efficacy in patients with schizophrenia. CNTRICS highlighted improving construct validation of tasks across species to increase the likelihood that the translation of a candidate molecule to humans will be successful. Other aspects of cross-species behaviors remain important however. This review describes cognitive tasks utilized across species, providing examples of differences and similarities of innate behavior between species, as well as convergent construct and predictive validity. Tests of attention, olfactory discrimination, reversal learning, and paired associate learning are discussed. Moreover, information on the practical implication of species differences in drug development research is also provided. The issues covered here will aid in task development and utilization across species as well as reinforcing the positive role preclinical research can have in developing procognitive treatments for psychiatric disorders.

► Cross-species translation is vital for the development of cognition enhancers. ► Ordinarily arguments are made for translatability (preclinical to clinic). ► Differences in cognition between species are discussed. ► From tests of attention, to reversal and paired associates learning. ► Practical implications of species differences on drug development also provided.