Prenatal stress generates deficits in rat social behavior: Reversal by oxytocin

Abstract

Neurodevelopmental changes induced by environmental stress exposure play a significant but poorly defined role in the etiology of schizophrenia. Exposure of pregnant female rats to a series of unpredictable stresses during the final week of pregnancy generates behavioral deficits and molecular changes in the offspring similar to those observed in schizophrenic individuals. We used this rat prenatal stress preparation to investigate social withdrawal behaviors that may have relevance to the negative symptoms of schizophrenia. The cumulative time adult male offspring of stress-exposed pregnant female rats actively interacted with a weight-matched, same-sex peer was decreased approximately 76% relative to non-stress exposed control rats. Prenatal stress exposure also diminished the quality of the social interaction behavior indicative of reduced social drive. Analysis of the oxytocinergic system in the prenatally stressed male rats revealed significantly less oxytocin mRNA in the paraventricular nucleus and increased oxytocin receptor binding in the central amygdala. Moreover, oxytocin, but not vasopressin, administration into the central amygdala reversed the social incompetence of the prenatally stressed rats without increasing behavior in nonstressed control animals. In addition, cross-fostering pups from prenatally stressed mothers to nonstressed mothers failed to improve the social deficit of the prenatally stressed male offspring. Two behavioral assays designed to measure anxiety did not differentiate the prenatally stressed rats from non-stressed controls. These data indicate that prenatal stress may be an etiologically appropriate animal model for some aspects of schizophrenic social withdrawal. Furthermore, unpredictable prenatal stress exposure selectively degrades social interaction behaviors without increasing anxiety measures.

Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms

“…A mutation may be inherited from parents or occur de novo. On the other hand, prenatal factors (like prenatal stressors [35] and drug abuse [36]) and the postnatal environment (like aberrant social environments [37]) may also lead to alteration of the OXT system, characterized by decreased central OXT mRNA levels and lower plasma OXT levels. Similar to OXT, studies on plasma AVP levels in ASD are limited and the results are controversial.…”

The Evolution of Drug Development in Schizophrenia: Past Issues and Future Opportunities

“…Second, schizophrenia is considered a polygenic disease and it is overly simplistic to think that knocking out a single gene will recreate the diverse phenotype manifest in schizophrenic patients. With regard to other models, the rat prenatal stress model has strong face and construct validity based on epidemiological findings associated with schizophrenia (Kinnunen et al, 2003;Koenig et al, 2005;Lee et al, 2007) and the rat neonatal ventral hippocampal lesion model appears to recreate many of the behaviors associated with schizophrenia. However, the limitation to this later preparation is the void created during the lesion process, the consequences of which have yet to be fully established (Lipska, 2004).…”

Efectos neurobiológicos del estrés prenatal sobre el nuevo ser

“…En ellos, se ha verificado que la exposición al estrés durante el embarazo y la privación materna al inicio de la vida postnatal, se asocia con conductas de tipo ansioso 19,20 , desregulación del eje HHA 21 , desarrollo neuronal alterado a nivel de hipocampo y amígdala 22 , déficits cognitivos 23 y comportamientos sociales desajustados en la descendencia 24 . Paralelamente, la investigación en humanos ha demostrado que el estrés materno y la ansiedad durante el embarazo también se vinculan con una alteración del neurodesarrollo infantil, incluyendo retraso en el desarrollo motor, deterioro cognitivo, alteraciones de la regulación emocional, temperamento difícil y síntomas del espectro del déficit atencional 25 .…”