research digest


We just had a paper on Conditioned Place Preference accepted in JPET with the Brennan lab at Queen Mary and Pfizer! We screened 27 drugs of varying human subjective effects and scheduling status for incentive value to assess the utility of zebrafish as a model for first round safety pharmacology. The findings reveal that zebrafish concordance and sensitivity values were not significantly different from chance for both positive human subjective effects and scheduling. Although significant improvements in specificity and negative predictive values were observed for zebrafish relative to positive human subjective effects, specificity without sensitivity provides limited predictive value. Moreover, assessments in zebrafish provided no added value for predicting scheduling. By contrast, rat and non-human primate models generally possessed significantly improved concordance, sensitivity, and positive predictive values for both clinical measures. While there may be predictive value with compounds from specific pharmacological classes (e.g. μ-opioid receptor agonists, CNS stimulants) for zebrafish CPP, altogether these data highlight that using the current methodology, the zebrafish CPP model does not add value to the preclinical assessment of abuse  potential. This research shows an important limitation of using 'lower' vertebrate models for SOME research questions; however, zebrafish have been very useful for looking at other aspects of addiction (underlying neural circuits, etc.) and more research is needed!!