HPA Axis Interactions with Behavioral Systems

Abstract

Perhaps the most salient behaviors that individuals engage in involve the avoidance of aversive experiences and the pursuit of pleasurable experiences. Engagement in these behaviors is regulated to a significant extent by an individual's hormonal milieu. For example, glucocorticoid hormones are produced by the hypothalamic-pituitary-adrenocortical (HPA) axis, and influence most aspects of behavior. In turn, many behaviors can influence HPA axis activity. These bidirectional interactions not only coordinate an individual's physiological and behavioral states to each other, but can also tune them to environmental conditions thereby optimizing survival. The present review details the influence of the HPA axis on many types of behavior, including appetitively-motivated behaviors (e.g., food intake and drug use), aversively-motivated behaviors (e.g., anxiety-related and depressive-like) and cognitive behaviors (e.g., learning and memory). Conversely, the manuscript also describes how engaging in various behaviors influences HPA axis activity. Our current understanding of the neuronal and/or hormonal mechanisms that underlie these interactions is also summarized. © 2016 American Physiological Society. Compr Physiol 6:1897-1934, 2016.

Figure 1)

Schematic summarizing the organization of the hypothalamic-pituitary-adrenocortical (HPA) axis. Upon activation, neurons in the paraventricular nucleus of the hypothalamus (PVH) release corticotropin releasing hormone (CRH) and other releasing factors into portal circulation. These releasing factors act on the anterior pituitary to stimulate the release of adrenocorticotropin hormone (ACTH) into systemic circulation. ACTH acts on the adrenal cortex to stimulate the release of glucocorticoids (GCs; cortisol for people and corticosterone for rodents) into the bloodstream. Additionally, the glucocorticoids exert negative feedback effects at the level of the brain/hypothalamus and anterior pituitary to constrain further HPA axis activity.

Figure 2)

Consumption of highly-palatable foods has opposing effects on hypothalamic-pituitary-adrenocortical (HPA) axis activity depending on the particular conditions surrounding the food intake. Eating small amounts of highly-palatable foods (particularly carbohydrates) in the context of a dietary choice reduces HPA axis tone. In contrast, eating large amounts of highly-palatable foods (particularly lipids) without a dietary choice generally leads to positive energy balance (e.g., obesity) and elevated HPA axis tone.

Figure 3)

Stress impacts most aspects of behavior, and the hypothalamic-pituitary-adrenocortical (HPA) axis is well-poised to mediate much of these stress effects. For example, HPA axis activation is linked with promoting aversively-motivated behaviors, appetitively-motivated behaviors, and learning and memory processes. In turn, when individuals respond to particular internal or external stimuli by evoking one of these various behaviors, HPA axis activity is also impacted. Other abbreviations shown on figure: ACTH – adrenocorticotropin hormone, CRH – corticotropin releasing hormone, GCs – glucocorticoids, GR – glucocorticoid receptor signaling.