TY - JOUR
T1 - Psychopharmacological effects of acute exposure to kynurenic acid (KYNA) in zebrafish
AU - Robinson, Kyle S.L.
AU - Stewart, Adam Michael
AU - Cachat, Jonathan
AU - Landsman, Samuel
AU - Gebhardt, Michael
AU - Kalueff, Allan V.
PY - 2013
Y1 - 2013
N2 - A metabolite of the kynurenine pathway, kynurenic acid (KYNA) is an important endogenous neuromodulator and neuroprotector, that also exerts neurotropic effects following exogenous administration. In humans and animals, KYNA regulates affective and cognitive responses, acting mainly as an antagonist of glutamatergic receptors. However, the complete psychopharmacological profile of KYNA (which includes the activity of several neurotransmitter receptors) is poorly understood, and merit further studies. Aquatic models are rapidly emerging as useful tools in translational psychopharmacology research. Here, we exposed adult zebrafish (Danio rerio) to exogenous KYNA for 20 min, and assessed their behavior in the novel tank test. Exposure to KYNA (20 mg/L) in this paradigm evoked overt effects in fish, including decreased latency to enter the top half of the tank, increased number of top entries and longer top duration. In contrast, locomotor activity indices (swimming distance and velocity) were not affected by KYNA in this study. Overall, our results show KYNA has an anxiolytic-like pharmacological effect in zebrafish, and therefore strongly support the utility of zebrafish models in neurotropic drug screening, including drugs acting at central glutamatergic system. Robust phenotypic differences evoked by KYNA, revealed here using three-dimensional (3D) reconstructions of zebrafish locomotion in X, Y and time (Z) coordinates, confirm this notion, also demonstrating the value of 3D-based phenotyping approaches for high-throughput drug screening using zebrafish models.
AB - A metabolite of the kynurenine pathway, kynurenic acid (KYNA) is an important endogenous neuromodulator and neuroprotector, that also exerts neurotropic effects following exogenous administration. In humans and animals, KYNA regulates affective and cognitive responses, acting mainly as an antagonist of glutamatergic receptors. However, the complete psychopharmacological profile of KYNA (which includes the activity of several neurotransmitter receptors) is poorly understood, and merit further studies. Aquatic models are rapidly emerging as useful tools in translational psychopharmacology research. Here, we exposed adult zebrafish (Danio rerio) to exogenous KYNA for 20 min, and assessed their behavior in the novel tank test. Exposure to KYNA (20 mg/L) in this paradigm evoked overt effects in fish, including decreased latency to enter the top half of the tank, increased number of top entries and longer top duration. In contrast, locomotor activity indices (swimming distance and velocity) were not affected by KYNA in this study. Overall, our results show KYNA has an anxiolytic-like pharmacological effect in zebrafish, and therefore strongly support the utility of zebrafish models in neurotropic drug screening, including drugs acting at central glutamatergic system. Robust phenotypic differences evoked by KYNA, revealed here using three-dimensional (3D) reconstructions of zebrafish locomotion in X, Y and time (Z) coordinates, confirm this notion, also demonstrating the value of 3D-based phenotyping approaches for high-throughput drug screening using zebrafish models.
KW - 3D reconstructions of locomotion
KW - Anxiety
KW - Kynurenic acid
KW - Novel tank test
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=84877638473&partnerID=8YFLogxK
U2 - 10.1016/j.pbb.2013.04.002
DO - 10.1016/j.pbb.2013.04.002
M3 - Article
C2 - 23583441
AN - SCOPUS:84877638473
SN - 0091-3057
VL - 108
SP - 54
EP - 60
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
ER -