Chemobehavioural phenomics and behaviour-based psychiatric drug discovery in the zebrafish.
Despite their ubiquity and impact, psychiatric illnesses and other disorders of the central nervous system remain among the most poorly treated diseases. Most psychiatric medicines were discovered due to serendipitous observations of behavioural phenotypes in humans, rodents and other mammals. Extensive behaviour-based chemical screens would likely identify novel psychiatric drugs. However, large-scale chemical screens in mammals are inefficient and impractical. In contrast, zebrafish are very well suited for high-throughput behaviour-based drug discovery. Furthermore, the vast amounts of data generated from large-scale behavioural screens in zebrafish will facilitate a systems-level analysis of how chemicals affect behaviour. Unlike serendipitous discoveries in mammals, a comprehensive and integrative analysis of zebrafish chemobehavioural phenomics may identify functional relationships that would be missed by more reductionist approaches. Thus, behaviour-based chemical screens in the zebrafish may improve our understanding of neurobiology and accelerate the pace of psychiatric drug discovery.
Kokel
David
D
Cardiovascular Research Center and Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA. dkokel@cvrc.mgh.harvard.edu
Peterson
Randall T
RT
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D055808:Drug Discovery; D015027:Zebrafish / Q000502:physiology*
D014150:Antipsychotic Agents
Epilepsia. 2007 Jun;48(6):1151-7
17521353
Nature. 2006 May 25;441(7092):451-6
16724057
Nat Biotechnol. 2004 Oct;22(10):1253-9
15470465
Psychiatr Q. 2006 Spring;77(1):43-53
16397754
Ann Surg. 1918 Jul;68(1):5-11
17863946
Pharmacogenet Genomics. 2007 Apr;17(4):237-53
17496723
J Exp Biol. 1977 Feb;66(1):65-81
870603
Neuropsychopharmacology. 2008 Apr;33(5):1206-15
17581529
Prog Neurobiol. 2002 Oct;68(2):85-111
12450489
Epilepsy Res. 2007 Jun;75(1):18-28
17485198
Naunyn Schmiedebergs Arch Pharmacol. 2007 Apr;375(2):81-4
17310263
J Hist Behav Sci. 2006 Fall;42(4):379-98
17024684
PLoS Genet. 2005 Nov;1(5):e66
16311625
J Neurosci. 2006 Dec 20;26(51):13400-10
17182791
Nat Chem Biol. 2008 Jan;4(1):33-41
18026094
Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):12965-9
11087852
Nature. 2005 Sep 22;437(7058):491-3
16177777
Nat Rev Drug Discov. 2007 Jul;6(7):521-32
17599084
Neurotoxicol Teratol. 2007 Nov-Dec;29(6):652-64
17761399
J Neurosci. 2005 Oct 5;25(40):9294-303
16207889
Nat Genet. 2003 May;34(1):15-21
12721547
Nat Chem Biol. 2005 Dec;1(7):366-70
16372403
Am J Psychiatry. 1958 Nov;115(5):459-64
13583250
Clin Pharmacol Ther. 2007 Jul;82(1):70-80
17495877
Nat Biotechnol. 2004 May;22(5):595-9
15097998
Circulation. 2003 Mar 18;107(10):1355-8
12642353
Proc Am Thorac Soc. 2007 Jan;4(1):18-25
17202287
Brain Behav Evol. 2002;60(4):207-29
12457080
Epilepsy Res. 2006 Jan;68(1):22-8
16377151
J Dev Behav Pediatr. 2002 Feb;23(1 Suppl):S51-6
11875291
Nat Med. 2004 Jul;10 Suppl:S51-7
15298008
Chem Biol Drug Des. 2006 Oct;68(4):213-9
17105485
J Neurosci. 2007 May 2;27(18):4984-94
17475807
J Exp Biol. 2007 Jul;210(Pt 14):2526-39
17601957
J Affect Disord. 2008 May;108(1-2):1-9
18001843
Psychiatr Serv. 1999 Jul;50(7):969
10402625
Neuroscience. 2005;131(3):759-68
15730879
Nat Rev Drug Discov. 2004 Apr;3(4):353-9
15060530
Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10545-9
7479837
Methods Cell Biol. 2004;76:569-91
15602893
Brain Res. 2001 Jun 8;903(1-2):263-8
11382414
Trends Pharmacol Sci. 2007 Nov;28(11):588-96
17963850
Nat Protoc. 2006;1(5):2448-51
17406490
J Neurosci. 1999 Oct 1;19(19):8603-15
10493760
Nat Rev Neurosci. 2006 Feb;7(2):137-51
16429123
Neurotoxicol Teratol. 2006 Mar-Apr;28(2):245-50
16527449
Nat Neurosci. 2004 May;7(5):462-6
15114359