Stress adaptation is of utmost importance for the maintenance of homeostasis and, therefore, of life itself. The prevalence of stress-related disorders is increasing, emphasizing the importance of exploratory research on stress adaptation. Two major regulatory pathways exist: the hypothalamic–pituitary–adrenocortical axis and the sympathetic adrenomedullary axis. They act in unison, ensured by the enormous bidirectional connection between their centers, the paraventricular nucleus of the hypothalamus (PVN), and the brainstem monoaminergic cell groups, respectively. PVN and especially their corticotropin-releasing hormone (CRH) producing neurons are considered to be the centrum of stress regulation. However, the brainstem seems to be equally important. Therefore, we aimed to summarize the present knowledge on the role of classical neurotransmitters of the brainstem (GABA, glutamate as well as serotonin, noradrenaline, adrenaline, and dopamine) in stress adaptation. Neuropeptides, including CRH, might be co-localized in the brainstem nuclei. Here we focused on CRH as its role in stress regulation is well-known and widely accepted and other CRH neurons scattered along the brain may also complement the function of the PVN. Although CRH-positive cells are present on some parts of the brainstem, sometimes even in comparable amounts as in the PVN, not much is known about their contribution to stress adaptation. Based on the role of the Barrington’s nucleus in micturition and the inferior olivary complex in the regulation of fine motoric—as the main CRH-containing brainstem areas—we might assume that these areas regulate stress-induced urination and locomotion, respectively. Further studies are necessary for the field.

Vasopressin is a ubiquitous molecule playing an important role in a wide range of physiological processes thereby implicated in the pathomechanism of many disorders. Its effect is well characterized through V2 receptors, which regulates the water resorption in kidney, while its vasoconstrictory effect through V1a receptor also received a lot of attention in the maintenance of blood pressure during shock. However, the most striking is its central effect both through the V1b receptors in stress-axis regulation as well as through V1a receptors regulating many aspects of our behavior (e.g., social behavior, learning and memory). Vasopressin has been implicated in the development of depression, due to its connection with chronic stress, as well as schizophrenia because of its involvement in social interactions and memory processes. Epigenetic changes may also play a role in the development of these disorders. The possible mechanism includes DNA methylation, histone modification and/or micro RNAs, and these possible regulations will be in the focus of our present review.