Population-dependent impacts of para-chlorophenylalanine, a tryptophan hydroxylase inhibitor, on homebase formation and thigmotaxis in adult zebrafish

Abstract

Alterations in monoamine levels, such as serotonin, play a role in the pathophysiology of affective disorders. Para-chlorophenylalanine (pCPA), a tryptophan hydroxylase inhibitor, impairs serotonin synthesis and increases anxiety-like behaviors in various species. Outbred zebrafish population, such as short fin (SF) and leopard (LEO), differ in serotonin expression, habituation patterns, and responses to novel environments. Locomotor and exploratory profiles are strongly influenced by homebase behavior, which can be assessed in the open field test (OFT). To further investigate a putative role of the serotoninergic system in homebase formation and exploratory behavior dynamics, we administered pCPA to two zebrafish populations (SF and LEO) with distinct anxiety profiles and homebase occupancy. Fish received intraperitoneal injections of pCPA (300 mg/kg) or vehicle for two consecutive days, followed by a 30-min OFT 24 h later. Both pCPA-treated populations showed increased locomotion and periphery occupancy was elevated during the habituation period (first 15 min of testing). Although pCPA did not alter homebase-related behaviors in LEO, the SF population exhibited a delayed homebase formation, likely due to disrupted exploratory-related mechanisms. Furthermore, Principal Component Analysis (PCA) and K-means clustering revealed that behaviors related to periphery occupancy and distance traveled accounted for approximately 80 % of the observed data variability. Collectively, our data show that pCPA impairs homebase formation, with stronger effects in SF fish and increases thigmotaxis. Overall, these results suggest that pCPA disrupts the organization of exploratory behavior, particularly the habituation processes, probably associated with anxiety-like phenotypes.