Addictions are chronic relapsing
brain diseases, with behavioral manifestations. Three main factors contribute to the development of an addiction: environment, including stress, the reinforcing effects of the
drug, and genetics. In this review we will discuss the involvement of the dysregulation of the stress responsive hypothalamic-pituitary-adrenal (HPA) axis in the acquisition of, and persistence to
drug addiction (Section B). Addictions to specific drugs such as
cocaine/psychostimulants, alcohol, and
mu-opioid receptor agonists (e.g.,
heroin) have some common direct or downstream effects, including modulation of dopaminergic systems. Through its action on the dopaminergic signaling pathways,
cocaine affects the HPA axis, and brain nuclei responsible for movements, and rewarding effects. Several neurobiological systems have been implicated with
cocaine addiction, including
dopamine,
serotonin and
glutamate systems,
opioid receptor and
opioid neuropeptide gene systems, stress-responsive systems including CRF,
vasopressin and
orexin. The use of animal models (Sections C and D) has been essential for studying the individual vulnerabilities to the effects of drugs of abuse and the neural pathways and
neurotransmitters affected by these drugs. Basic clinical research has revealed important relationship between
cocaine use, HPA axis responsiveness, and gender (Section E). Finally, we will discuss gene polymorphisms that are associated with
drug use (Section F). Results from animal models and basic clinical research have shown important interactions between the dopaminergic and the
opioid systems. Hence, compounds modulating the
opioid system may be beneficial in treating
cocaine addiction.