Stress, Adaptation, and Disease: Allostasis and Allostatic Load

McEwen, Bruce S.

doi:10.1111/j.1749-6632.1998.tb09546.x

Cited by 3,972 publications

(3,222 citation statements)

References 53 publications

Supporting

Mentioning

2,947

Contrasting

Unclassified

Order By: Relevance

“…Allostatic load as defined by McEwen and Stellar (1993) refers to the cost or the price the body may have to pay for being forced to adapt to an adverse or deleterious psychological or physical situation, and it represents the presence of too much demand on the operation of the regulatory systems -mainly the primary mediators of the physiological response -or their failure to relax when the demand is over. Different types of allostatic load have been considered that may explain different types or gradients of morbidity (McEwen 1998a). Whatever the modality, the process is translated into a different structural-functional state (i.e., a vulnerable phenotype).…”

Section: Allostasismentioning

confidence: 99%

“…A state of stress is associated with various external and internal challenges to the body and brain, usually termed stressors, and the construct of stress may represent the extreme pathological continuum of overactivation of the normal activational (arousal) or emotional systems of the body (Hennessy and Levine 1979). Such arousal-activational mechanisms trigger biological and behavioral strategies of coping and control that mobilize many organismic and central nervous system mechanisms, whose failure leads to illness (McEwen 1998a;Schulkin et al 1994;Sterling and Eyer 1981). The state of stress is reflected biologically by various physiological changes that include an activation of the pituitary-adrenal axis and release of glucocorticoids into the bloodstream (Stanford and Salmon 1993), activation of the sympathetic nervous system, and activation of brain emotional systems.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Drug Addiction, Dysregulation of Reward, and Allostasis

Koob

Moal

2001

Neuropsychopharmacology

2,561

1,962

View full text Add to dashboard Cite

This paper reviews recent developments in the neurocircuitry and neurobiology of addiction from a perspective of allostasis. A model is proposed for brain changes that occur during the development of addiction that explain the persistent vulnerability to relapse long after drug-taking has ceased. Addiction is presented as a cycle of spiralling dysregulation of brain reward systems that progressively increases, resulting in the compulsive use and loss of control over drug-taking. The development of addiction recruits different sources of reinforcement, different neuroadaptive mechanisms, and different neurochemical changes to dysregulate the brain reward system. Counteradaptive processes such as opponent-process that are part of normal homeostatic limitation of reward function fail to return within the normal homeostatic range and are hypothesized to form an allostatic state. Allostasis from the addiction perspective is defined as the process of maintaining apparent reward function stability by changes in brain reward mechanisms. The allostatic state represents a chronic deviation of reward set point and is fueled not only by dysregulation of reward circuits per se, but also by the activation of brain and hormonal stress responses. The manifestation of this allostatic state as compulsive drugtaking and loss of control over drug-taking is hypothesized to be expressed through activation of brain circuits involved in compulsive behavior such as the cortico-striatal-thalamic loop. The view that addiction is the pathology that results from an allostatic mechanism using the circuits established for natural rewards provides a realistic approach to BACKGROUNDDrug addiction is a chronically relapsing disorder that is defined by two major characteristics: a compulsion to take the drug with a narrowing of the behavioral repertoire toward excessive drug intake, and a loss of control in limiting intake (American Psychiatric Association 1994; World Health Organization 1992). An important challenge for neurobiological research is to understand the neuroadaptive differences between controlled drug use and loss of control, and by extension, the molecular, cellular and system processes that lead to addiction (Koob and Le Moal 1997).Animal models are critical for understanding the neuropharmacological mechanisms involved in the development of addiction. While there are no complete animal models of addiction, animal models do exist for many elements of the syndrome. These elements can be derived from symptoms or diagnostic criteria for addiction or conceptual frameworks such as different sources of reinforcement (American Psychiatric Association 1994; World Health Organization 1992). Linking neu- 24 , NO . 2 ropharmacological events to animal models can occur at multiple levels of analysis -molecular, cellular and system -and it will only be the integration of these changes across dimensions of analysis that will allow a full understanding of the neurobiology of drug addiction.Advances in neuroscience research are rapidly unr...

show abstract

Section: Allostasismentioning

confidence: 99%

mentioning

confidence: 99%

Drug Addiction, Dysregulation of Reward, and Allostasis

Koob

Moal

2001

Neuropsychopharmacology

2,561

1,962

View full text Add to dashboard Cite

show abstract

“…6 adversity, compromising the ability of the organism to manage stress (McEwen, 1998;Taylor, 2010). Alternatively, the "match-mismatch" models predict that after a juvenile stress experience, individuals will show improvements in coping behavior and adaptability to further exposures to stress in adulthood (Claessens et al, 2011;Oitzl et al, 2010;Schmidt, 2011).…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Behavioral and neuroendocrine consequences of juvenile stress combined with adult immobilization in male rats

Fuentes

Carrasco

Armario

et al. 2014

Hormones and Behavior

View full text Add to dashboard Cite

Exposure to stress during childhood and adolescence increases vulnerability to developing several psychopathologies in adulthood and alters the activity of the hypothalamic-pituitaryadrenal (HPA) axis, the prototypical stress system. Rodent models of juvenile stress appear to support this hypothesis because juvenile stress can result in reduced activity/exploration and enhanced anxiety, although results are not always consistent. Moreover, an in-depth characterization of changes in the HPA axis is lacking. In the present study, the long-lasting effects of juvenile stress on adult behavior and HPA function were evaluated in male rats. The juvenile stress consisted of a combination of stressors (cat odor, forced swim and footshock) during postnatal days 23-28. Juvenile stress reduced the maximum amplitude of the adrenocorticotropic hormone (ACTH) levels (reduced peak at lights off), without affecting the circadian corticosterone rhythm, but other aspects of the HPA function (negative glucocorticoid feedback, responsiveness to further stressors and brain gene expression of corticotrophin-releasing hormone and corticosteroid receptors) remained unaltered. The behavioral effects of juvenile stress itself at adulthood were modest (decreased activity in the circular corridor) with no evidence of enhanced anxiety. Imposition of an acute severe stressor (immobilization on boards, IMO) did not increase anxiety in control animals, as evaluated one week later in the elevated-plus maze (EPM), but it potentiated the acoustic startle response (ASR). However, acute IMO did enhance anxiety in the EPM, in juvenile stressed rats, thereby suggesting that juvenile stress sensitizes rats to the effects of additional stressors.

show abstract

“…In particular, much attention is focusing on physiological dysregulation (alternatively referred to as allostatic load or homeostenosis) (McEwen, 1998; Karlamangla et al ., 2002; Crimmins et al ., 2003). While evidence is abundant for increases in various types of physiological dysfunction with age, our use of ‘dysregulation’ is more restricted, as an emergent property of a complex system in the formal sense (Holland, 1992; Kauffman, 1993; Kriete, 2013).…”

Section: Introductionmentioning

confidence: 99%

Homeostatic dysregulation proceeds in parallel in multiple physiological systems

et al. 2015

View full text Add to dashboard Cite

SummaryAn increasing number of aging researchers believes that multi‐system physiological dysregulation may be a key biological mechanism of aging, but evidence of this has been sparse. Here, we used biomarker data on nearly 33 000 individuals from four large datasets to test for the presence of multi‐system dysregulation. We grouped 37 biomarkers into six a priori groupings representing physiological systems (lipids, immune, oxygen transport, liver function, vitamins, and electrolytes), then calculated dysregulation scores for each system in each individual using statistical distance. Correlations among dysregulation levels across systems were generally weak but significant. Comparison of these results to dysregulation in arbitrary ‘systems’ generated by random grouping of biomarkers showed that a priori knowledge effectively distinguished the true systems in which dysregulation proceeds most independently. In other words, correlations among dysregulation levels were higher using arbitrary systems, indicating that only a priori systems identified distinct dysregulation processes. Additionally, dysregulation of most systems increased with age and significantly predicted multiple health outcomes including mortality, frailty, diabetes, heart disease, and number of chronic diseases. The six systems differed in how well their dysregulation scores predicted health outcomes and age. These findings present the first unequivocal demonstration of integrated multi‐system physiological dysregulation during aging, demonstrating that physiological dysregulation proceeds neither as a single global process nor as a completely independent process in different systems, but rather as a set of system‐specific processes likely linked through weak feedback effects. These processes – probably many more than the six measured here – are implicated in aging.

show abstract

Stress, Adaptation, and Disease: Allostasis and Allostatic Load

Cited by 3,972 publications

References 53 publications

Drug Addiction, Dysregulation of Reward, and Allostasis

Drug Addiction, Dysregulation of Reward, and Allostasis

Behavioral and neuroendocrine consequences of juvenile stress combined with adult immobilization in male rats

Homeostatic dysregulation proceeds in parallel in multiple physiological systems

Contact Info

Product

Resources

About