Excessive dopamine release in the mesocorticolimbic system |
Adult |
Pharmacological → Enhancing dopamine (D2) neurotransmission |
Also tested with chronic administration |
Lodge & Grace, 20081616. Lodge DJ, Grace AA. Hippocampal dysfunction and disruption of dopamine system
regulation in an animal model of schizophrenia. Neurotox Res. 2008;14:97-104.
|
Reduced glutamatergic activity |
Adult |
Pharmacological → NMDA antagonists (ketamine, PCP, MK801) |
Also tested with neonatal ketamine administration |
Javitt et al., 20121717. Javitt DC, Zukin SR, Heresco-Levy U, Umbricht D. Has an angel shown the
way? Etiological and therapeutic implications of the PCP/NMDA model of schizophrenia. Schizophr
Bull. 2012;38:958-66.
|
Serotonergic system malfunction |
Adult |
Pharmacological → Psychedelic drugs (LSD) |
Models the hallucinatory aspect of psychosis |
Moreno et al., 20131818. Moreno JL, Holloway T, Umali A, Rayannavar V, Sealfon SC, González-Maeso J.
Persistent effects of chronic clozapine on the cellular and behavioral responses to LSD in mice.
Psychopharmacology (Berl). 2013;225:217-26.
|
Brain connectivity abnormalities |
Neonatal (PN7) |
Lesion → of the ventral hippocampus (NVHL model) |
Models the delayed onset of schizophrenia |
Tseng et al., 20091919. Tseng KY, Chambers RA, Lipska BK. The neonatal ventral hippocampal lesion as a
heuristic neurodevelopmental model of schizophrenia. Behav Brain Res.
2009;204:295-305.
|
Epigenetic control of development |
Prenatal (GD17) |
Toxin → MAM |
MAM is a strong methylating agent (possible role of DNA methylation) |
Peleg-Raibstein et al., 20122020. Peleg-Raibstein D, Feldon J, Meyer U. Behavioral animal models of antipsychotic
drug actions. Handb Exp Pharmacol. 2012;212:361-406.
|
Shaping of brain development by the environment |
Weaning to adulthood |
Social isolation |
Could be mediated by oxidative stress |
Fabricius et al., 20112121. Fabricius K, Helboe L, Fink-Jensen A, Wörtwein G, Steiniger-Brach B.
Pharmacological characterization of social isolation-induced hyperactivity. Psychopharmacology
(Berl). 2011;215:257-66.
|
Mother-pup interaction shaping brain development |
Weaning to adulthood |
Neonatal isolation (PN9) |
Potential contribution of the brain-neurovegetative system interplay |
De la Fuente et al., 20092222. De la Fuente M, Llorente R, Baeza I, De Castro NM, Arranz L, Cruces J, et al.
Early maternal deprivation in rats: a proposed animal model for the study of developmental
neuroimmunoendocrine interactions. Ann N Y Acad Sci. 2009;1153:176-83.
|
Genetic determinism of schizophrenia |
Genetic |
Knockout of DISC1 (disrupted gene in schizophrenia) |
Rare human mutation enhancing the incidence of some diseases |
Jaaro-Peled; 20092323. Jaaro-Peled H. Gene models of schizophrenia: DISC1 mouse models. Prog Brain Res.
2009;179:75-86.
|
Neuronal migration, altered synaptogenesis |
Genetic |
Reelin-deficient mouse |
Reelin gene found reduced in patients with schizophrenia |
Laviola et al., 20092424. Laviola G, Ognibene E, Romano E, Adriani W, Keller F. Gene-environment
interaction during early development in the heterozygous reeler mouse: clues for modelling of major
neurobehavioral syndromes. Neurosci Biobehav Rev. 2009;33:560-72.
|
Modified dopamine neurotransmission |
Genetic |
Dopamine transporter knockout |
Also produces a cholinergic deficit |
Weiss et al., 20072525. Weiss S, Tzavara ET, Davis RJ, Nomikos GG, Michael McIntosh J, Giros B, et al.
Functional alterations of nicotinic neurotransmission in dopamine transporter knock-out mice.
Neuropharmacology. 2007;52:1496-508.
|
Metabotropic glutamate receptor alteration |
Genetic |
mGluR5 knockout |
Belongs to the models pointing to altered glutamatergic system |
Wierońska et al., 20122626. Wierońska JM, Stachowicz K, Acher F, Lech T, Pilc A. Opposing efficacy of
group III mGlu receptor activators, LSP1-2111 and AMN082, in animal models of positive symptoms of
schizophrenia. Psychopharmacology (Berl). 2012;220:481-94.
|
Dysfunctional neurotransmission |
Genetic |
Sandy “sdy” mouse (knockout of dysbindin-1) |
Affects dopaminergic, GABAergic, and glutamatergic transmission |
Talbot, 20092727. Talbot K. The sandy (sdy) mouse: a dysbindin-1 mutant relevant to schizophrenia
research. Prog Brain Res. 2009;179:87-94.
|
Reduced growth factor production |
Every age |
BDNF overexpression by stress |
Found altered in some disorders |
Fumagalli et al., 20122828. Fumagalli F, Calabrese F, Luoni A, Bolis F, Racagni G, Riva MA. Modulation of
BDNF expression by repeated treatment with the novel antipsychotic lurasidone under basal condition
and in response to acute stress. Int J Neuropsychopharmacol. 2012;15:235-46.
|
Viral infection/brain inflammation |
Prenatal (PN18) |
Infection |
Possible role of hyperthermia |
Winter et al., 20082929. Winter C, Reutiman TJ, Folsom TD, Sohr R, Wolf RJ, Juckel G, et al. Dopamine and
serotonin levels following prenatal viral infection in mouse--implications for psychiatric disorders
such as schizophrenia and autism. Eur Neuropsychopharmacol . 2008;18:712-6.
|
Brain inflammation |
Prenatal (or early postnatal) |
Immune stimulation by LPS injection |
Immune-inflammatory parameters altered in several mental disorders |
Elovitz et al., 20113030. Elovitz MA, Brown AG, Breen K, Anton L, Maubert M, Burd I. Intrauterine
inflammation, insufficient to induce parturition, still evokes fetal and neonatal brain injury. Int
J Dev Neurosci. 2011;29:663-71.
|
Mild chronic stress leads to depression |
Adult |
Application of mild electric shocks chronically |
Decreases sucrose preference or engagement in sexual behavior (anhedonia?) |
Willner, 200599. Willner P. Chronic mild stress (CMS) revisited: consistency and
behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology.
2005;52:90-110.
|
Circadian rhythms and their related genes are involved in mania |
Genetic |
Study of mice with polymorphisms in CLOCK gene |
Affects dopamine and produces decreased sleep, hypophagia, hyperlocomotion, and risk-taking
behavior |
Roybal et al., 20071414. Roybal K, Theobold D, Graham A, DiNieri JA, Russo SJ, Krishnan V, et al.
Mania-like behavior induced by disruption of CLOCK. Proc Natl Acad Sci U S A.
2007;104:6406-11.
|