Stress and the Body's Response

by National Institute of Health

(Page 2 of 6)

The term "stress" generally refers to the reactions of the body to certain events or stimuli that the organism perceives as potentially harmful or distressful. Such stressinducing events or stimuli, which are referred to as stressors, can be either physical (unusual environmental conditions or a physical attack) or psychological (occupational or familial difficulties) in nature. Individual people respond differently to different stressors. An event that is perceived as extremely stressful by one person may be perceived as harmless by another.

Whenever an organism perceives a situation as stressful, it initiates a stress response - that is, a complex spectrum of behavioral reactions, such as escape or avoidance behaviors; biological reactions, such as increases in heart rate, blood pressure, or sweating; and (in humans) emotional reactions, such as feelings of anxiety. The stress response is coordinated through two mechanisms: 1. changes in the activities of various brain regions and brain chemicals (neurotransmitters) and 2. changes in the activity of a hormonal system called the hypothalamic-pituitary-adrenal (HPA) axis. Neurotransmitters involved in controlling the stress response include serotonin, dopamine, and opioid peptides. These neurotransmitter systems act through a variety of mechanisms. Thus, opioid peptides directly lead to pain relief, and dopamine release results in increases in blood pressure and heart rate. Furthermore, various neurotransmitters can affect the body more indirectly by inhibiting or enhancing the activity of the HPA axis.

The HPA axis consists of three hormones: 1. corticotropin-releasing hormone (CRH), which is produced in a brain region called the hypothalamus; 2. adrenocorticotropic hormone (ACTH), which is released from the pituitary gland located below the hypothalamus; and 3. glucocorticoid hormones, which are secreted from the adrenal glands located on top of the kidneys. The three types of hormones form a tightly regulated hormone cascade. Activation of various nerve cells (neurons) in the brain in response to stress results in the production and release of CRH from certain cells in the hypothalamus. Through specific blood vessels in the brain, CRH is transported from the hypothalamus to the pituitary gland, where it induces the production and secretion of ACTH into the body's general circulation. Through the blood, ACTH reaches the adrenal glands and initiates the production and release of glucocorticoid hormones. (The major glucocorticoid in humans is cortisol, whereas the major glucocorticoid in rodents is corticosterone.) These glucocorticoids induce and regulate the body's diverse physiological responses to stress, such as changes in cardiovascular function and sweat gland activity.

The activity of the HPA axis is regulated by a negative feedback mechanism in which glucocorticoids released into circulation act back on the hypothalamus and/or pituitary gland to suppress further release of CRH and/or ACTH.

The body's neurochemical and hormonal responses to stress do not act independently of each other, but are tightly interconnected. Thus, CRH release in the hypothalamus is regulated by neurons releasing serotonin or endogenous opioids. Furthermore, CRH release not only results in ACTH release, but also in the release of certain endogenous opioids from specific neurons in the brain, which may contribute to various behavioral and emotional consequences of stress.

Neurobiological Connections Between Stress and Addiction

Animal studies have suggested that exposure to stress facilitates both the initiation and the reinstatement of AOD use after a period of abstinence. To better understand the biological basis of the effects of stress on AOD self-administration in animals, researchers have focused primarily on two neurobiological systems. The first system involves the organism's hormonal and subsequent biological responses to stress and the influence of those responses on the reinforcing effects of AODs. Those studies, which aim mainly to identify specific, stress-induced hormonal changes that mediate the effects of stress on AOD self-administration, primarily have examined the activity of a hormone system called the hypothalamic-pituitary-adrenal (HPA) axis. This hormone system has three components:

Corticotropin-releasing hormone (CRH), which is produced in a brain region called the hypothalamus

Adrenocorticotropic hormone (ACTH), which is produced in the pituitary gland located in the brain below the hypothalamus

Glucocorticoid hormones, such as cortisol in humans and corticosterone in rodents, which are produced in the adrenal glands that are located on top of the kidneys.

Glucocortocoid secretion by the adrenal gland is considered one of the central biological responses to stressful events. Studies have shown that both acute stress and alcohol or cocaine administration can activate the HPA axis, probably by acting on CRH. Consistent with this hypothesis, agents that interfere with CRH function also decrease sensitivity to environmental stress in animal models and prevent some of the reinforcing effects of cocaine.

The second neurobiological system investigated in animal studies of stress and AOD use involves the stress-induced changes in the activity of certain brain regions and brain molecules (neurotransmitters) assumed to play a role in mediating the reinforcing effects of AODs. This approach is based on the hypothesis that stress facilitates AOD self-administration in laboratory animals and humans by enhancing the activity of those neurobiological systems. This research has focused mostly on nerve cells (neurons) that are located in the midbrain (mesencephalon) and which use the neurotransmitter dopamine. Some of these neurons extend to the nucleus accumbens, which is considered one of the primary brain areas involved in mediating the reinforcing effects of various AODs.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.