Cross-talk between the HPA axis and addiction-related regions in stressful situations

Addiction is a worldwide problem that has a negative impact on society by imposing significant costs on health care, public security, and the deactivation of the community economic cycle. Stress is an important risk factor in the development of addiction and relapse vulnerability. Here we review studies that have demonstrated the diverse roles of stress in addiction. Term searches were conducted manually in important reference journals as well as in the Google Scholar and PubMed databases, between 2010 and 2022. In each section of this narrative review, an effort has been made to use pertinent sources. First, we will provide an overview of changes in the Hypothalamus-Pituitary-Adrenal (HPA) axis component following stress, which impact reward-related regions including the ventral tegmental area (VTA) and nucleus accumbens (NAc). Then we will focus on internal factors altered by stress and their effects on drug addiction vulnerability. We conclude that alterations in neuro-inflammatory, neurotrophic, and neurotransmitter factors following stress pathways can impact related mechanisms on craving and relapse susceptibility.