Integration of the circadian and stress systems: influence of neuropeptides and implications for alcohol consumption

Disruptions in circadian rhythm and stress reactivity are associated with risks of developing neuropsychiatric disorders. The circadian system is organised in a hierarchical manner, whereby the master clock is located at the suprachiasmatic nucleus, a highly conserved brain region that coordinates the oscillations of peripheral clocks. Exposure to psychological stress leads to activation of the hypothalamic-pituitary-adrenal axis. There is growing evidence supporting the interactions between the circadian and stress systems. Anatomically, the circadian and stress signals converge at the paraventricular nucleus (PVN) in the hypothalamus. Genes that are involved in the operation of the circadian and stress systems, including Clock, Period and CRH are expressed in the PVN. In addition, several neuropeptides, including arginin-vasopressin, vasoactive intestinal polypeptide, pituitary adenylate cyclase-activating polypeptide and the neurotransmitter gamma-aminobutyric acid, are present in the PVN. In this review, we will discuss the interaction of circadian genes and stress-response genes at the molecular, neurotransmission and behavioural levels. We will place particular emphasis on the role of neuropeptides in mediating this interaction.