title: The effects of cocaine on heart rate and electrocardiogram in zebrafish (Danio rerio).
abstract: Zebrafish (Danio rerio) have been used as a model organism to explore the genetic basis for responsiveness to addictive drugs like cocaine. However, very little is known about how the physiological response to cocaine is mediated in zebrafish. In the present study electrocardiograms (ECGs) were recorded from adult zebrafish treated with cocaine. Treatment with cocaine resulted in a bell-shaped dose response curve with a maximal change in heart rate seen using 5mg/L cocaine. Higher doses resulted in a higher percentage of fish showing bradycardia. The cocaine-induced tachycardia was blocked by co-treatment with propranolol, a β-adrenergic antagonist, but potentiated by co-treatment with phentolamine, an α-adrenergic antagonist. Co-treatment with atropine, a classic cholinergic antagonist, had no effect on cocaine-induced tachycardia. Cocaine treatment of adult fish changed the ECG of treated fish, inducing a dose-dependent increase in QT interval after adjusting for heart rate (QTc), while not affecting the PR or QRS intervals. The acute effects of cocaine on heart rate were examined in 5-day old embryos to see if zebrafish might serve as a suitable model organism to study possible links of embryonic physiological response to subsequent adult behavioral response to the drug. Cocaine treatment of 5-day old zebrafish embryos also resulted in a bell-shaped dose response curve, with maximal tachycardia achieved with 10mg/L. The response in embryonic fish was thus comparable to that in adults and raises the possibility that the effects of embryonic exposure to cocaine on the developing cardiovascular system can be effectively modeled in zebrafish.
authors.affiliation: University of North Dakota, Biology Department, Grand Forks, ND 58202-9019, USA.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Mersereau
authors.affiliation: University of North Dakota, Biology Department, Grand Forks, ND 58202-9019, USA.
authors.forename: Shelby L
authors.initials: SL
authors.lastname: Poitra
authors.affiliation: University of Arizona, Department of Ecology and Evolutionary Biology, Tucson, AZ 85721, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Espinoza
authors.affiliation: University of North Texas, Department of Biological Sciences, Denton, TX 76203, USA.
authors.forename: Dane A
authors.initials: DA
authors.lastname: Crossley
authors.affiliation: University of North Dakota, Biology Department, Grand Forks, ND 58202-9019, USA. Electronic address: tristan.darland@und.edu.
authors.forename: Tristan
authors.initials: T
authors.lastname: Darland
mesh_terms: D000818:Animals; D003042:Cocaine / Q000633:toxicity*; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D004562:Electrocardiography / Q000187:drug effects*; D004625:Embryo, Nonmammalian / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D015027:Zebrafish
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine
keywords: Adrenergic compounds; Cocaine; Electrocardiogram; Heart rate; Zebrafish
references.citation: Circulation. 1999 Aug 3;100(5):497-502
references.pmid: 10430763
references.citation: Am J Physiol Heart Circ Physiol. 2006 Jul;291(1):H269-73
references.pmid: 16489111
references.citation: J Am Coll Cardiol. 2007 Aug 14;50(7):626-33
references.pmid: 17692748
references.citation: Circulation. 2008 Feb 19;117(7):866-75
references.pmid: 18250272
references.citation: Ann Biomed Eng. 2009 May;37(5):890-901
references.pmid: 19280341
references.citation: Clin Cardiol. 2010 May;33(5):264-9
references.pmid: 20513064
references.citation: Neurobiol Dis. 2010 Oct;40(1):66-72
references.pmid: 20493262
references.citation: Zebrafish. 2010 Sep;7(3):297-304
references.pmid: 20807039
references.citation: Circulation. 2010 Dec 14;122(24):2558-69
references.pmid: 21156654
references.citation: Exp Clin Psychopharmacol. 2011 Oct;19(5):321-41
references.pmid: 21843010
references.citation: Methods Mol Biol. 2012;843:11-20
references.pmid: 22222517
references.citation: Neuroscience. 2012 Apr 5;207:182-97
references.pmid: 22300980
references.citation: Hum Genet. 2012 Jun;131(6):977-1008
references.pmid: 22207143
references.citation: Pharmacol Biochem Behav. 2012 Dec;103(2):157-67
references.pmid: 22910534
references.citation: J Pharmacol Toxicol Methods. 2013 Mar-Apr;67(2):115-20
references.pmid: 23353637
references.citation: Anat Rec. 2001 Sep 1;264(1):1-12
references.pmid: 11505366
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11691-6
references.pmid: 11553778
references.citation: Psychopharmacology (Berl). 2002 Sep;163(2):221-9
references.pmid: 12202969
references.citation: Circulation. 2003 Mar 18;107(10):1355-8
references.pmid: 12642353
references.citation: Eur J Pharmacol. 1975 Sep-Oct;33(2):313-7
references.pmid: 171163
references.citation: Clin Exp Hypertens. 1978;1(2):141-65
references.pmid: 39712
references.citation: Pharmacol Biochem Behav. 1988 Jan;29(1):157-62
references.pmid: 3353421
references.citation: Comp Biochem Physiol C. 1989;92(1):149-53
references.pmid: 2566437
references.citation: Am J Cardiol. 1989 Jun 15;63(20):1529-30
references.pmid: 2729144
references.citation: Circ Res. 1989 Jul;65(1):185-92
references.pmid: 2736735
references.citation: J Pharmacol Exp Ther. 1990 Feb;252(2):491-9
references.pmid: 1968971
references.citation: J Clin Invest. 1991 Apr;87(4):1322-8
references.pmid: 2010545
references.citation: Circulation. 1992 Feb;85(2):407-19
references.pmid: 1346509
references.citation: Drug Alcohol Depend. 1995 Mar;37(3):217-30
references.pmid: 7796716
references.citation: Development. 1996 Dec;123:285-92
references.pmid: 9007248
references.citation: Eur J Pharmacol. 1998 Dec 18;363(2-3):147-52
references.pmid: 9881582
references.citation: Pharmacol Biochem Behav. 2005 Sep;82(1):90-7
references.pmid: 16112720
references.citation: J Exp Biol. 2005 Mar;208(Pt 5):821-9
references.pmid: 15755880