Genetic Transmission of Behavior and Its Neuroendocrine Correlates

Profound dysfunctions in diverse neuroendocrine systems have been described in psychiatric patients suffering from affective disorders such as anxiety and major depression (MD). In order to elucidate the mechanisms underlying these functional alterations, animal models, including mice that are genetically modified by either direct gene-targeting or by selective breeding approaches, have been more often used, revealing valuable insights into neuroendocrine pathways conserved between rodents and men. In this chapter we focus on altered function and regulation of the hypothalamic–pituitary–adrenocortical (HPA) axis, including its involvement in emotionality and stress responsiveness. In this context, the corticotropin-releasing hormone system and disturbances in glucocorticoid receptor signaling seem to be of central importance. However, changes in the expression and release patterns of vasopressin and oxytocin have also been shown to contribute profoundly to behavioral alterations including emotionality, stress coping, and social behaviors. Furthermore, substantial anxiogenic and nociceptive effects have been described for neurokinin receptors activated by tachykinins. Finally, signaling through opioid receptors was shown to be strongly involved in nociception, reward, anxiety-related and depression-like behaviors upon binding of β-endorphin, dynorphin, or enkephalin. Thus, research involving animal models and neuropeptide systems significantly contributes to our understanding regarding the transmission of genetic predispositions into clinically relevant neuroendocrine and behavioral endophenotypes.