A state of threatened HOMEOSTASIS brought on by repeated exposure to an AVERSIVE STIMULUS or other threat. Stress-inducing stimuli are commonly referred to as STRESSORS and include physical (for example, extreme cold or heat) and psychological threat (for example, dismay at the loss of one’s job). Walter Cannon (1871–1945) introduced the term stress response in the early 1900s to refer to an animal’s response to stressors. Animals, including humans, react to stressors by activating a complex array of responses in the body which include a combination of cognitive (negative emotions), physiological, endocrine, and immunological responses (McEwen & Sapolsky, 1995). Alterations in the ability of the organism to respond to stressors, with the responses being either excessive or inadequate in magnitude and duration, may lead eventually to a myriad of different disease states including psychiatric risk (for instance acute onset SCHIZOPHRENIA), cardiovascular disorders, GASTRIC ulcers, and reduced resistance to infections (for instance autoimmunity diseases). The magnitude of stress responses are determined by a multiplicity of factors, including the type of stressor and length of exposure, the individual’s developmental history and genetic makeup, and strategies that the individual adopts to cope with the stress.
Threatening stressful situations generally evoke vigorous activity and activate various AUTONOMIC and ENDOCRINE responses that assist to mobilize the body’s ENERGY resources. Under these conditions, activation of the autonomic SYMPATHETIC NERVOUS SYSTEM results in the secretion of the HORMONES, ADRENALINE (epinephrine) and (norepinephrine) from the medulla (core) of the ADRENAL GLAND. Adrenaline affects GLUCOSE metabolism, causing nutrients stored in muscles to become available as an energy source for strenuous exercise. Adrenaline, together with noradrenaline, also increases blood pressure and blood flow to muscles. Over the long term, stress-related elevations in circulating blood concentrations of these hormones may contribute to cardiovascular disease. Stressors can also activate neurons in the central nucleus of the AMYGDALA, a component of the LIMBIC SYSTEM known to play a role in EMOTION. The central nucleus of the amygdala sends a projection to the PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS to signal the secretion of the peptide neurohormone CORTICOTROPIN RELEASING FACTOR (CRF). CRF may act as a neuromodulator/neurotransmitter (see NEUROMODULATION/NEUROTRANSMITTERS) at sites in the brain involved in emotional responses, such as the PERIAQUEDUCTAL GREY and the LOCUS COERULEUS, including the central nucleus of the amygdala. Secretion of CRF from the paraventricular nucleus of the hypothalamus stimulates the anterior PITUITARY GLAND to secrete ADRENOCORTICOTROPIC HORMONE (ACTH). In turn, ACTH enters the circulatory system to activate the release of steroid stress hormones called GLUCOCORTICOIDS (such as CORTISOL) from the cortex (shell) of the adrenal gland. Glucocorticoids assist in the catabolism of PROTEINS and conversion to glucose, help in utilization of FAT as an energy source in the body, increase blood flow, and stimulate behavioural responses.
The increased fuel supply to cells enables them to sustain a high level of activity in the face of stress. They also decrease the sensitivity of the GONADS to LUTEINIZING HORMONE which, in turn, suppresses the secretion of steroid SEX HORMONES.
Experimental evidence suggests that prolonged secretion of glucocorticoids represents the most harmful effects of stress. Long-term effects of glucocorticoids on the body include increased blood pressure, damage to muscle tissue, steroid DIABETES, infertility, acceleration of the AGEING process, inhibition of developmental growth, inhibition of the inflammatory responses, and the suppression of the IMMUNE SYSTEM. Stress-induced elevations in brain levels of glucocorticoids has also been linked to damage to brain regions involved in LEARNING and MEMORY (cells in the CA1 field of the HIPPOCAMPUS for example). These cells appear highly susceptible to changes in energy metabolism. Cortisol treatments effectively decrease the ability of these neurons to utilize glucose, such that when blood flow decreases to a critical level these cells die. Animal investigations of stress have also implicated central DOPAMINE systems in the neurochemistry of the stress response. Stress-inducing procedures used in the rodent model include IMMOBILIZATION, TAIL-PINCH, and inescapable electric FOOTSHOCK. These procedures have been paired with previously neutral stimuli (a tone for example) which after several pairings can elicit a stress response on its own—this is fear conditioning. These procedures have proven useful for studying neurochemical correlates of stress apart from physical PAIN and have been shown to decrease activity of TUBEROHYPOPHYSEAL DOPAMINE SYSTEM and the TUBEROINFUNDIBULAR DOPAMINE SYSTEM. In contrast, midbrain dopamine neurons projecting to the OLFACTORY TUBERCLE, amygdala, NUCLEUS ACCUMBENS, STRIATUM and PREFRONTAL CORTEX are activated by mild stressors. The selective response of MESOLIMBICOCORTICAL SYSTEM to mild stressors may be ‘associated with either an emotional state of anxiety or a coping response in reaction to that emotional state’ (Horger & Roth, 1996).
