Acute administration of a dopamine D2/D3 receptor agonist alters behavioral and neural parameters in adult zebrafish

Abstract

AbstractThe dopaminergic neurotransmitter system is involved in numerous brain functions and behavioral processes. Alterations in this neurotransmitter system are associated with the pathogenesis of several human neurological disorders. Pharmacological agents that interact with the dopaminergic system allow the investigation of dopamine-mediated cellular and molecular responses and may elucidate the biological bases of such disorders. The zebrafish, a translationally relevant biomedical research organism, has been successfully employed in prior psychopharmacology studies. Here, we evaluate the effects of quinpirole (a dopamine D2/D3 receptor agonist) in adult zebrafish on behavioral parameters and neurotransmitter levels. Adult zebrafish received intraperitoneal injections of 0.5, 1.0, or 2.0 mg/kg of quinpirole or saline (control group) twice with an inter-injection interval of 48h. All tests were performed 24h after the second injection. After acute quinpirole administration, zebrafish exhibited decreased locomotor activity, increased anxiety-like behaviors and memory impairment compared to control. However, the quinpirole administration did not affect social and aggressive behavior. Quinpirole-treated fish exhibited altered swimming patterns: fish showed stereotypic swimming characterized by repetitive behavior, swimming from corner to corner at the bottom of the tank preceded and followed by episodes of immobility. Moreover, analysis of neurotransmitter levels in the brain demonstrated a significant increase in glutamate and a decrease in serotonin, while no alterations were observed in dopamine. These findings demonstrate that dopaminergic signaling altered by quinpirole administration results in significant changes in behavior and neurotransmitter levels in the central nervous system of zebrafish. Thus, we conclude that the use of quinpirole administration in adult zebrafish may be an appropriate tool for the analysis of mechanisms underlying neurological disorders related to the dopaminergic system.