Developing translational animal models for symptoms of schizophrenia or bipolar mania.
Animal models have long been used to explore hypotheses regarding the neurobiological substrates of and treatments for psychiatric disorders. Early attempts to develop models that mimic the entirety of the diagnostic syndromes in psychiatry have evolved into more appropriate efforts to model specific symptoms. Such an approach reflects the facts that even in patients, clinical symptoms transcend diagnostic categories, and the specific etiologies of psychiatric disorders are unknown. An animal model can only be identified adequately by specifying both the manipulation (drug, lesion, strain) used to induce abnormalities and the measure(s) used to characterize them. A wide range of pharmacological, lesion, and developmental manipulations have been combined with various measures of information processing to develop useful animal models that parallel human tests. Prepulse inhibition of startle, event-related potential (ERP) measures of auditory gating, and Cambridge neuropsychological test automated battery (CANTAB) measures of cognition are examples of measures that can be used in both rodents and humans and that are robustly altered in both psychiatric disorders and animals manipulated with appropriate drugs or lesions. The further development of cross-species models is critically important, given the new opportunities for the development and registration of specific treatments for the cognitive disorders of schizophrenia that are not ameliorated by available drugs. In moving beyond the focus on psychotic symptoms to the cognitive symptoms of schizophrenia, animal models that do not involve manipulations of dopamine D(2) receptors but that do utilize information processing measures that are correlated with cognitive disturbances are receiving increased attention. Here, selected examples of how cross-species measures of psychiatric disorders are developed and validated are discussed. Specific animal paradigms that parallel the specific domains of cognition that are altered in schizophrenia provide one focus of the review. Another focus includes efforts to develop new human models of psychiatric symptoms that are designed to parallel existing tests used in rodents.
Geyer
M A
MA
Department of Psychiatry, University of California San Diego, La Jolla, CA 92093-0804, USA. mgeyer@ucsd.edu
D000818:Animals; D001714:Bipolar Disorder / Q000150:complications*; D003072:Cognition Disorders / Q000209:etiology*; D004195:Disease Models, Animal; D006801:Humans; D012559:Schizophrenia / Q000150:complications*
Psychopharmacology (Berl). 2003 Sep;169(3-4):365-6
12955292
Schizophr Bull. 2005 Oct;31(4):830-53
16177277
Schizophr Bull. 2005 Oct;31(4):888-94
16079387
Dialogues Clin Neurosci. 2006;8(1):9-16
16640109
Biol Psychiatry. 1999 Mar 1;45(5):551-8
10088045
Psychopharmacology (Berl). 2001 Jul;156(2-3):194-215
11549223
Am J Psychiatry. 1999 Jul;156(7):1046-51
10401450
Neuropsychopharmacology. 2006 Nov;31(11):2349-58
16855533
J Psychopharmacol. 2006 Sep;20(5):714-22
16401660
Neuropsychopharmacology. 2006 Sep;31(9):2011-21
16482083
Biol Psychiatry. 2006 Sep 15;60(6):597-603
16997001
Neuropsychopharmacology. 2008 Feb;33(3):497-512
17460616
Psychopharmacology (Berl). 2001 Jul;156(2-3):284-90
11549230
Neurosci Biobehav Rev. 2006;30(4):456-71
16253329
Psychopharmacology (Berl). 2001 Jul;156(2-3):234-58
11549226
Pharmacol Biochem Behav. 1993 Mar;44(3):741-4
8451276
Schizophr Res. 2004 Dec 15;72(1):41-51
15531406
Schizophr Bull. 1999;25(2):233-55
10416729
Biol Psychiatry. 2003 Jul 15;54(2):121-8
12873801
Pharmacol Biochem Behav. 1986 Jul;25(1):277-88
2875472
Neurosci Biobehav Rev. 2001 Jul;25(5):409-26
11566479
Neurosci Biobehav Rev. 2007;31(6):882-96
17706782
Schizophr Res. 2004 Dec 15;72(1):5-9
15531402
Schizophr Res. 2004 Dec 15;72(1):29-39
15531405
Curr Opin Psychiatry. 2007 Jan;20(1):1-7
17143074
Psychopharmacology (Berl). 2001 Jul;156(2-3):273-83
11549229
Biol Psychiatry. 2001 Sep 15;50(6):418-24
11566158
Am J Psychiatry. 1996 Mar;153(3):321-30
8610818
Mol Psychiatry. 2002;7(10):1039-53
12476318
J Pharmacol Exp Ther. 1990 Aug;254(2):456-64
1974635
Psychopharmacology (Berl). 2001 Jul;156(2-3):117-54
11549216
Neurotox Res. 2002 Aug-Sep;4(5-6):489-502
12754162
Psychopharmacology (Berl). 2004 Jun;174(1):54-64
15205879
Behav Neurosci. 2000 Apr;114(2):374-88
10832798
Arch Gen Psychiatry. 1990 Feb;47(2):181-8
2405807
Behav Brain Res. 2007 Aug 6;181(2):278-86
17559953
Prog Neuropsychopharmacol Biol Psychiatry. 2003 Oct;27(7):1071-9
14642967
Psychopharmacology (Berl). 2005 Jun;180(1):57-62
15650841