To Model a Psychiatric Disorder in Animals Schizophrenia As a Reality Test

Abstract

Animal modeling has been instrumental in dissectingAnimal models are important developments in investigations of the mechanisms underlying a human disease and the design of new treatments. This is true for many diseases, but generally not for mental disorders, whose modeling in experimental animals has often been regarded as a highly controversial or outright heretic idea. An example of a particularly formidable challenge for animal modeling is schizophrenia, a complex disorder of unknown origin, characterized by abnormalities of uniquely human behaviors in the realms of perception, thinking and the experience of emotions, and whose onset is virtually restricted to young adulthood. Schizophrenia is such an inherently human disease that reproducing its most prominent symptoms-hallucinations, delusions and thought disorder-in a rodent or even in a non-human primate seems doomed. However, recent new evidence about the neurobiology of the condition has generated new avenues of animal research. In this perspective article, we highlight recent achievements in the efforts to model the neurobiology of schizophrenia in animals, consider limitations inherent in any heuristic animal model of this and probably other psychiatric disorders, and discuss the usefulness of a new generation of animal models for testing particular hypotheses about etiology and pathophysiology of schizophrenia.

Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling

“…16,42 For example, deficits in sensorimotor gating, as evident in reduced PPI, is observed in a number of neuropsychiatric disorders, including schizophrenia, 29 schizotypal personality disorder, 43 autism 30 and obsessivecompulsive disorder. 44 On the other hand, impaired selective associative learning in the form of disrupted LI has been observed in a subset of schizophrenic patients, especially in those suffering acutely from positive symptoms.…”

Prenatal Immune Challenge Disrupts Sensorimotor Gating in Adult Rats Implications for the Etiopathogenesis of Schizophrenia

“…Although no animal model can fully reproduce the perceptual, cognitive and emotional features of the human illness (Lipska and Weinberger 2000), the prenatal immune challenge model here described, based on a hypothetical causative factor in schizophrenia, reproduces to some extent behavioral and biological phenomena relevant to schizophrenia: (1) Prenatally LPS-exposed rats displayed a clear sensorimotor gating deficit, which, being qualitatively similar to the disturbance seen in schizophrenic patients, is overcome by antipsychotic treatment. (2) Several histopathological alterations are observed in brain areas directly related to the sensorimotor gating circuitry, and, to some extent, resemble those described in schizophre-nia.…”

Effect of Dopamine D3 Antagonists on PPI in DBA/2J Mice or PPI Deficit Induced by Neonatal Ventral Hippocampal Lesions in Rats

“…Another recently developed nonpharmacological model, which also exhibits a fair degree of validity to several aspects of schizophrenia, is the 'neonatal ventral hippocampal (NVH) lesion-induced deficits' model proposed by Lipska and co-workers as offering a valid simulation of psychosis disorders (Lipska et al, 2002(Lipska et al, , 1993Lipska and Weinberger, 2000). Indeed, NVH-lesioned rats showed behavioral deficits resembling several aspects of schizophrenia.…”