Alcohol and the Hypothalamic-Pituitary-Adrenal-Axis

 The health of mammals depends on their ability to maintain the internal environment of their bodies within narrow and clearly defined limits in the face of physiological or psychological threats. Challenges to the body's homeostasis—whether perceived or real—are handled by the hypothalamic-pituitary- adrenal (HPA) axis, which involves the interaction of the brain structure known as the hypothalamus, the pituitary gland (just below the hypothalamus) and the adrenal glands (at the top of the kidneys). Together, these three organs control reactions to stress and regulate many body processes, including digestion, the immune system, mood and emotions, sexuality, as well as energy storage and expenditure.

Alcohol is one of the stimuli that activate the HPA axis in rodents, but the mechanisms responsible for it are not yet fully understood. Rivier's laboratory had shown earlier that the peptide corticotropin-releasing factor (CRF), which is produced in the hypothalamus, was essential for an appropriate HPA axis response to acute alcohol. While the ultimate effect of alcohol is the binding of CRF to specific receptors on pituitary cells, and the ensuing release of ACTH and adrenal steroids, recent experiments by Rivier and her team revealed a more complex picture of alcohol's action on the brain. They found that alcohol increases the activity of dopamine b-hydroxylase, the enzyme directly responsible for the synthesis of norepinephrine. The latter contributes to the HPA axis's response to alcohol, and this knowledge may help the development of specific therapies that counteract some of the deleterious effects of this drug.

Stress is thought to play a role in the ability of addicted individuals to maintain abstinence. Thus, a better understanding of the function of the HPA axis during the development of alcohol dependence, and how the activity of this axis differs between dependent and non-dependent animals, will be helpful in pursuing novel therapies for the treatment of alcohol addiction.