Influence of stress associated with chronic alcohol exposure on drinking.
paper
Cited
Public
- Authors
- Becker, Howard C
- Year
- 2017
- Journal
- Neuropharmacology
- PMID
- 28431971
- DOI
- 10.1016/j.neuropharm.2017.04.028
- PMCID
- PMC5497303
Stress is commonly regarded as an important trigger for relapse and a significant factor that promotes increased motivation to drink in some individuals. However, the relationship between stress and alcohol is complex, likely changing in form during the transition from early moderated alcohol use to more heavy uncontrolled alcohol intake. A growing body of evidence indicates that prolonged excessive alcohol consumption serves as a potent stressor, producing persistent dysregulation of brain reward and stress systems beyond normal homeostatic limits. This progressive dysfunctional (allostatic) state is characterized by changes in neuroendocrine and brain stress pathways that underlie expression of withdrawal symptoms that reflect a negative affective state (dysphoria, anxiety), as well as increased motivation to self-administer alcohol. This review highlights literature supportive of this theoretical framework for alcohol addiction. In particular, evidence for stress-related neural, physiological, and behavioral changes associated with chronic alcohol exposure and withdrawal experience is presented. Additionally, this review focuses on the effects of chronic alcohol-induced changes in several pro-stress neuropeptides (corticotropin-releasing factor, dynorphin) and anti-stress neuropeptide systems (nocicepton, neuropeptide Y, oxytocin) in contributing to the stress, negative emotional, and motivational consequences of chronic alcohol exposure. Studies involving use of animal models have significantly increased our understanding of the dynamic stress-related physiological mechanisms and psychological underpinnings of alcohol addiction. This, in turn, is crucial for developing new and more effective therapeutics for treating excessive, harmful drinking, particularly stress-enhanced alcohol consumption. This article is part of the Special Issue entitled "Alcoholism".
Stress Influences on the Progression of Alcohol Addiction.When drinking is first initiated and regulated, alcohol and stress interact in a complex manner. Stress may promote alcohol consumption via glucocorticoid interactions with brain reward systems and, for some individuals, the anxiolytic (stress-alleviating) effect alcohol may influence motivation to drink. Continued heavy drinking results in fundamental changes in brain function. Under assault from continued alcohol exposure, the brain engages a host of adaptations in brain reward and stress systems that contribute to the perpetuation of excessive levels of drinking. Stress associated with heavy bouts of drinking and repeated failed attempts at abstinence fuel progressive dysregulation of these brain systems beyond normal homeostatic limits, setting the stage for a persistent dysfunctional (allostatic) state. This is characterized by exaggerated neuroadaptations that manifest as reduced reward processing, a blunted neuroendocrine stress response, engagement of extra-hypothalamic stress (e.g., CRF, dynorphin) and anti-stress (e.g., nociceptin, NPY, oxytocin) systems, and heightened autonomic nervous system (sympathomimetic) function. Collectively, these changes contribute to a persistent negative emotional (affective) state along with compromised executive function that renders individuals ill-equipped to exert appropriate behavioral control over alcohol consumption, as well as appropriately respond to stressful events that may provoke return to excessive drinking.
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| 20 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.1 Corticotropin-Releasing Factor (CRF) | al., 2016). Overall, while a role for CRF2 receptors cannot be ruled out (Funk and Koob, 2007;β¦ |
| 21 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.2 Dynorphin | Because both stress and chronic alcohol engage the DYN/KOR system, the role of this neuropeptideβ¦ |
| 22 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.2 Dynorphin | to reward and stress circuitries involved in alcohol/drug addiction (Shirayama et al., 2004).β¦ |
| 23 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.2 Dynorphin | Structures within the extended amygdala circuitry that are intimately involved in mediating negativeβ¦ |
| 24 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.2 Dynorphin | by direct injection of a KOR antagonist into the CeA (Kissler et al., 2014) or into the nucleusβ¦ |
| 25 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.2 Dynorphin | There is also evidence for interaction between the DYN/KOR system and CRF within extended amygdalaβ¦ |
| 26 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.3 Other Stress-Related Neuropeptides | Aside from CRF and DYN, several other neuropeptide systems in brain are involved in stress responseβ¦ |
| 27 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.3 Other Stress-Related Neuropeptides β 4.3.1 Nociceptin | Nociceptin/orphanin FQ is a 17-amino acid peptide classified as being a member of the opioid family,β¦ |
| 28 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.3 Other Stress-Related Neuropeptides β 4.3.1 Nociceptin | withdrawal-related anxiety and drinking. For example, infusion of nociceptin into brain ventriclesβ¦ |
| 29 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.3 Other Stress-Related Neuropeptides β 4.3.1 Nociceptin | Contrary to these findings, recent reports suggest that blocking, rather than activating, NOPβ¦ |
| 30 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.3 Other Stress-Related Neuropeptides β 4.3.2 Neuropeptide Y | Neuropeptide Y (NPY) is known to mediate anti-stress effects, typically opposing behavioral actionsβ¦ |
| 31 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.3 Other Stress-Related Neuropeptides β 4.3.2 Neuropeptide Y | Pharmacological studies also support a role for NPY in the regulation of alcohol consumption,β¦ |
| 32 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.3 Other Stress-Related Neuropeptides β 4.3.2 Neuropeptide Y | finding was reported in mice (Sparrow et al., 2012), corroborating results from a study showingβ¦ |
| 33 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.3 Other Stress-Related Neuropeptides β 4.3.2 Neuropeptide Y | Studies have shown that chronic alcohol exposure alters NPY function and this may contribute toβ¦ |
| 34 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.3 Other Stress-Related Neuropeptides β 4.3.3 Oxytocin | A growing body of literature suggests that oxytocin plays a significsant role in alcohol (and otheβ¦ |
| 35 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.3 Other Stress-Related Neuropeptides β 4.3.3 Oxytocin | Preclinical evidence indicates that oxytocin influences a number of behavioral and physiologicalβ¦ |
| 36 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.3 Other Stress-Related Neuropeptides β 4.3.3 Oxytocin | Oxytocin is known to exert stress-bufferring effects, and this may be of relevance to its role inβ¦ |
| 37 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.4 Glucocorticoids | Alcohol-induced activation of the HPA axis results in elevated circulating glucocorticoids and itβ¦ |
| 38 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.4 Glucocorticoids | Stress associated with chronic alcohol exposure and withdrawal results in a dysregulated HPA axis.β¦ |
| 39 | 4. Mechanisms Underlying Chronic Alcohol, Stress, and Drinking Relationship β 4.4 Glucocorticoids | There is also evidence that chronic alcohol exposure alters corticosteroid levels and glucocorticoidβ¦ |
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