Role of various neurotransmitters in mediating the long-term endocrine consequences of prenatal alcohol exposure.

Adult rats and mice born to dams exposed to alcohol (fetal alcohol-exposed [FAE]) exhibit enhanced activity of their hypothalamic-pituitary-adrenal (HPA) axis when exposed to stressors. However, the mechanisms responsible for this phenomenon remain incompletely understood. Here two possibilities are reviewed: one that pertains to nitric oxide (NO), an unstable gas that stimulates the HPA axis; and one that focuses on catecholamines, which also stimulate this axis. Significant alterations were not observed in levels of NO synthase, the enzyme responsible for NO formation, in the paraventricula nucleus (PVN) of FAE rats. However, the stimulatory influence of this gas on the hypothalamic-pituitary-adrenal (HPA) axis was enhanced in these animals, thereby providing a mechanism likely to participate in the neuroendocrine hyperactivity that is the hallmark of this model. It was also recently shown that, while the ability of catecholamines to release adrenocorticotropic hormone (ACTH) was comparable in control rats and rats exposed to alcohol during embryonic development, there was a significant upregulation of the C1 brain-stem region when these latter animals were exposed to mild footshocks. Since this region sends prominent projections to the PVN, its increased activity may participate in the HPA axis hyperactivity observed in FAE offspring. Finally, microarray technology was used to search for potential differences in genes present in the brains of control and FAE mice. When these brains were collected on day 17.5 of embryonic development, several genes were upregulated, while others were downregulated, which may provide potential new candidates that mediate the influence of prenatal alcohol on the HPA axis of adult offspring.