TITLE:
Genetic Rat Models of Schizophrenia-Relevant Symptoms
AUTHORS:
Cristóbal del Río, Ignasi Oliveras, Toni Cañete, Gloria Blázquez, Adolf Tobeña, Alberto Fernández-Teruel
KEYWORDS:
Schizophrenia, Genetic Rat Models, Selective Breeding, Prepulse Inhibition, Dopamine, Serotonin, Glutamate
JOURNAL NAME:
World Journal of Neuroscience,
Vol.4 No.3,
June
26,
2014
ABSTRACT:
It is recognized that developing valid animal models is essential for the
research on the neurobiological mechanisms of (and treatments for) psychiatric
disorders, even when these are as complex as schizophrenia. To be considered a
valid analogue of the disorder, a given model should present good face validity
(i.e. similarity of symptoms), good
predictive validity (i.e. similarity
of treatment effects and potential for discovering novel treatments) and enough
construct validity (i.e. the model
should help discover neurobiological mechanisms underlying the disorder or some
relevant symptoms). The complexity of symptoms (positive, negative and
cognitive) of schizophrenia makes it a very difficult task for a model to mimic
all the main features of the disorder, but some rodent (mouse and rat) models
have behavioural and even neurobiological phenotype characteristics resembling
positive-like symptoms, cognitive symptoms and some neurochemical features of
schizophrenia. As several recent works have already reviewed the main
behavioural and developmental models, as well as the most used drug-induced,
lesion-induced and genetic mouse models, the present review focuses on
describing the most relevant genetically-based rat models of schizophrenia-relevant
symptoms. Thus, we discuss several selective breeding programs leading to rat
lines/strains which present impaired prepulse inhibition (PPI) of the acoustic
startle response and (in some cases) latent inhibition deficits (both of which
may be considered as endophenotypes of
schizophrenia related with pre-attentive processes and attention, respectively),
as well as other schizophrenia-relevant symptoms (e.g. learning deficits).
Evidence is presented for the effects of genetic background on PPI (and other
symptoms/phenotypes), as well as for environmental influences on genetic
predisposition to enhanced apomorphine (mixed dopamine receptor agonist)
effects. Some of the described rat models appear to present face validity and,
to a certain extent, construct validity. While efforts should be made to
evaluate the predictive validity of these genetic rat models, we propose that
they have the advantage (over mouse knockouts, for example) of better
representing “normal” genetic, neurobiological and phenotype variation, thus
allowing the study of associations among them by means of genetic mapping or
gene expression studies.