Abstract
Psychiatric disorders are multifactorial diseases with etiology that may involve genetic factors, early life environment and stressful life events. The neurodevelopmental hypothesis of schizophrenia is based on a wealth of data on increased vulnerability in individuals exposed to insults during the perinatal period. Maternal deprivation (MD) disinhibits the adrenocortical response to stress in neonatal rats and has been used as an animal model of schizophrenia. To test if long-term affective consequences of early life stress were influenced by maternal presence, we submitted 10-day old rats, either deprived (for 22 h) or not from their dams, to a stress challenge (i.p. saline injection). Corticosterone plasma levels were measured 2 h after the challenge, whereas another subgroup was assessed for behavior in the open field, elevated plus maze (EPM), social investigation and the negative contrast sucrose consumption test in adolescence (postnatal day 45). Maternally deprived rats exhibited increased plasma corticosterone (CORT) levels which were higher in maternally deprived and stress challenged pups. Social investigation was impaired in maternally deprived rats only, while saline injection, independently of MD, was associated with increased anxiety-like behavior in the EPM and an impaired intake decrement in the negative sucrose contrast. In the open field, center exploration was reduced in all maternally-deprived adolescents and in control rats challenged with saline injection. The most striking finding was that exposure to a stressful stimulus per se, regardless of MD, was linked to differential emotional consequences. We therefore propose that besides being a well-known and validated model of schizophrenia in adult rats, the MD paradigm could be extended to model early signs of psychiatric dysfunction, and would particularly be a useful tool to detect early signs that resemble schizophrenia.
Highlights
Mental illnesses are among the most frequent causes of functional debilitation
The saline injection on PND10 resulted in increased anxietylike behavior and impairment in the sucrose negative contrast test (SNCT)
There was no evidence of interaction between these two early events, inasmuch as Maternal deprivation (MD) STR neonates presented a four-fold increase in CORT levels after the saline injection compared to MD UNS rats, but behaviorally these groups exhibited similar alterations
Summary
Mental illnesses are among the most frequent causes of functional debilitation. Schizophrenia is a markedly devastating psychiatric disorder, affecting approximately 1% of the global population (Freedman, 2003). It is challenging to precisely outline the causes of schizophrenia, because a multitude of genetic and environmental factors are thought to interact in the course of the disease, resulting in the onset, maintenance and evolution of schizophrenic symptoms (for a review on the multifactorial aspect of mental disorders, see Akdeniz et al, 2014; Uher, 2014). One of the most explored aspects on the environment-gene interaction prompting schizophrenic phenotype is the impact of harsh early life conditions, leading to the neurodevelopmental hypothesis of schizophrenia (Fatemi and Folsom, 2009; Piper et al, 2012), which postulates that neurochemical disturbances induced by adverse early life events could permanently affect brain function, producing abnormalities that would underlie the emergence of the disorder. Animal models are imperative to comprehend how early life adverse events affect behavioral and neurobiological aspects that reflect the basic underpinnings of mental disorders such as schizophrenia
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