Acute Citalopram administration modulates anxiety in response to the context associated with a robotic stimulus in zebrafish

Background: Anxiety represents one of the most urgent health challenges in Western Countries, where it is associated with major medical and societal costs. A common therapeutic approach is the use of selective serotonin reuptake inhibitors, such as Citalopram. However, this treatment of choice is characterized by incomplete efficacy and potential side effects. Preclinical research is needed to detail the mechanisms underlying therapeutic efficacy of available treatments. Methods: Zebrafish, a rapidly emerging model species, constitutes an excellent candidate for high-throughput studies in behavioral pharmacology. Here, we present a robotics-based experimental paradigm to investigate the effects of acute Citalopram administration on conditioned place aversion. We trained adult subjects in a three-partitioned tank, consisting of one central and two lateral compartments: the latter were associated either with a fear eliciting robotic stimulus or with an empty environment. Following training, we implemented an automated three-dimensional tracking system to assess the spatial association and detail individual phenotype in a stimulus-free test session. Results: We observed a linear dose-response profile with respect to geotaxis, with increasing Citalopram concentrations reducing the tendency to swim near the bottom of the tank. Although control subjects failed to exhibit the predicted conditioned aversion, we found preliminary evidence that Citalopram may affect sexes differentially, with male subjects showing increased conditioned aversion at low Citalopram concentration. Conclusions: Experimental paradigms based on robotics and three-dimensional tracking can contribute methodological advancements in zebrafish behavioral psychopharmacology.