Lateral amygdaloid nucleus expansion in adult rats is associated with exposure to prenatal stress.

ABSTRACT

Anxiety disorders in humans have been associated with chronic activation of the hypothalamic-pituitary-adrenal axis and changes in the volume of the amygdala. Interest in the etiology of anxiety disorders has led us and others to investigate the effects of prenatal stress on the brain development of adult male rat offspring. Prenatally stressed rats represent a promising animal model for anxiety disorders in that they have already been characterized as having both upregulated corticotropin-releasing factor (CRF) brain biochemistry and altered, more fearful, behaviors. Consistent with this, there is now evidence that prenatal stress also has an impact on the development of CRFergic neurons in the hypothalamic paraventricular nucleus and neurogenesis in the hippocampus. At this time, little information about the impact of prenatal stress on amygdala anatomy has been presented. Here we asked whether prenatal stress also has an impact on the development of the amygdala, because this structure plays a direct role in the emotions of anxiety and fear. Stereological measures of well-defined subregions of amydgdaloid nuclei revealed significantly expanded dimensions of the lateral nucleus in prenatally stressed offspring, due, in part, to more neurons and glia. These data may have direct import for the effect of adverse early life experiences and the etiology of anxiety disorders in humans. They also imply that early experiences may not be "grown out of" with development; in fact, the opposite might be true-adverse early life experiences may set developmental events into motion in the brain that last a lifetime.