title: Behavioral effects of bidirectional modulators of brain monoamines reserpine and d-amphetamine in zebrafish.
abstract: Brain monoamines play a key role in the regulation of behavior. Reserpine depletes monoamines, and causes depression and hypoactivity in humans and rodents. In contrast, d-amphetamine increases brain monoamines' levels, and evokes hyperactivity and anxiety. However, the effects of these agents on behavior and in relation to monoamine levels remain poorly understood, necessitating further experimental studies to understand their psychotropic action. Zebrafish (Danio rerio) are rapidly emerging as a promising model organism for drug screening and translational neuroscience research. Here, we have examined the acute and long-term effects of reserpine and d-amphetamine on zebrafish behavior in the novel tank test. Overall, d-amphetamine (5 and 10mg/L) evokes anxiogenic-like effects in zebrafish acutely, but not 7 days later. In contrast, reserpine (20 and 40 mg/L) did not evoke overt acute behavioral effects, but markedly reduced activity 7 days later, resembling motor retardation observed in depression and/or Parkinson's disease. Three-dimensional 'temporal' (X, Y, time) reconstructions of zebrafish locomotion further supports these findings, confirming the utility of 3D-based video-tracking analyses in zebrafish models of drug action. Our results show that zebrafish are highly sensitive to drugs bi-directionally modulating brain monoamines, generally paralleling rodent and clinical findings. Collectively, this emphasizes the potential of zebrafish tests to model complex brain disorders associated with monoamine dysregulation.
authors.affiliation: Zebrafish Neuroscience Research Consortium (ZNRC) and ZENEREI Institute, 309 Palmer Court, Slidell, LA 70458, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Kyzar
authors.forename: Adam Michael
authors.initials: AM
authors.lastname: Stewart
authors.forename: Samuel
authors.initials: S
authors.lastname: Landsman
authors.forename: Christopher
authors.initials: C
authors.lastname: Collins
authors.forename: Michael
authors.initials: M
authors.lastname: Gebhardt
authors.forename: Kyle
authors.initials: K
authors.lastname: Robinson
authors.forename: Allan V
authors.initials: AV
authors.lastname: Kalueff
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology*; D015027:Zebrafish
chemical_list: D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D012110:Reserpine; D003913:Dextroamphetamine
keywords: Anxiety; D-amphetamine; Depression; Locomotor activity; Monoamine; Novel tank test; Reserpine; Zebrafish