Neural Pathways of Stress Integration

Stress is a critical component in the development, maintenance, and reinstatement of addictive behaviors, including alcohol use. This article reviews the current state of the literature on the brain's stress response, focusing on the hypothalamic-pituitary- adrenal (HPA) axis. Stress responses can occur as a reaction to physiological (or systemic) challenge or threat; signals from multiple parts of the brain send input to the paraventricular nucleus (PVN) within the hypothalamus. However, responses also occur to stressors that predict potential threats (psychogenic stressors). Psychogenic responses are mediated by a series of nerve cell connections in the limbic-PVN pathway, with amygdalar and infralimbic cortex circuits signaling excitation and prelimbic cortex and hippocampal neurons signaling stress inhibition. Limbic-PVN connections are relayed by predominantly GABAergic neurons in regions such as the bed nucleus of the stria terminalis and preoptic area. Chronic stress affects the structure and function of limbic stress circuitry and results in enhanced PVN excitability, although the exact mechanism is unknown. Of importance, acute and chronic alcohol exposure are known to affect both systemic and psychogenic stress pathways and may be linked to stress dysregulation by precipitating chronic stress-like changes in amygdalar and prefrontal components of the limbic stress control network.