Alcohol, stress, and glucocorticoids: From risk to dependence and relapse in alcohol use disorders - PubMed (original) (raw)

Review

Alcohol, stress, and glucocorticoids: From risk to dependence and relapse in alcohol use disorders

Sara K Blaine et al. Neuropharmacology. 2017.

Abstract

In this review, we detail the clinical evidence supporting the role of psychological and physiological stress in instrumental motivation for alcohol consumption during the development of mild to moderate alcohol use disorders (AUDs) and in the compulsive, habitual alcohol consumption seen in severe, chronic, relapsing AUDs. Traditionally, the study of AUDs has focused on the direct and indirect effects of alcohol on striatal dopaminergic pathways and their role in the reinforcing effects of alcohol. However, growing evidence also suggests that alcohol directly stimulates the hypothalamic pituitary adrenal (HPA) axis and has effects on glucocorticoid receptors in extrahypothalamic, limbic forebrain, and medial Prefrontal Cortex (PFC) circuits, which contribute to the development of AUDs and their progression in severity, chronicity, and relapse risk. Evidence indicates HPA axis, glucocorticoid, and PFC dysfunction during protracted withdrawal and under high arousal conditions in those with severe AUDs, and novel evidence is also emerging to suggest HPA axis dysfunction with binge/heavy drinking, which is associated with motivation for alcohol in non-dependent individuals. Specifically, alcohol-associated alterations in HPA axis responses to stress and alcohol cues may serve as interoceptive physiological signals and facilitate conditioning mechanisms to influence alcohol motivation. Thus, this dysfunction may serve as a potential biomarker of both risk and of relapse. Based on this emerging data, we conceptualize and present early evidence for treatment targets that may improve PFC function and/or normalize HPA axis functioning and may be beneficial in the treatment and relapse prevention of AUDs. Finally, we suggest that individual differences in alcohol-related pathophysiology in these circuits may modulate treatment and recovery response, thereby supporting the need for building personalized medicine algorithms to understand and treat AUDs. This article is part of the Special Issue entitled "Alcoholism".

Keywords: Alcohol relapse; Alcoholism; Compulsive motivation; HPA axis; Prefrontal cortex; Stress.

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Figures

Figure 1

Specific regions of the corticolimbic striatal circuitry that are influenced by alcohol (in blue) and by stress (in red) to identify the overlapping hypothalamic and extra-hypothalamic brain pathways underlying stress, reward, and motivation.

Figure 2

The relationship of simultaneous measurement of cortisol during brief sustained stress exposure relative to no-stress neutral exposure with key corticolimbic-striatal brain regions are shown. Correlation images from whole brain regression analysis showing association between stress-neutral (S-N) brain activity and cortisol response (S-N) are shown in A (p<0.05, whole brain corrected). Corresponding scatterplots from extracted beta weights of key corticostriatal-limbic regions of interest (ROIs) indicate areas of association from the S-N regression map and the S-N cortisol responses are shown in B. Red/yellow, positive correlation; blue/purple, negative correlation. (Reproduced with permission from Sinha et al., 2016, Proceedings of the National Academy of Sciences).

Figure 3

Whole brain correlation between disrupted adrenal sensitivity (Cortisol:ACTH ratio) and VmPFC and ventral striatal dysfunction during neutral (tonic) and stress (phasic) responses in 4-week abstinent recovering alcoholics. Both responses predicted future return to alcohol intake (Reproduced with permission from Blaine et al., Addiction Biology, 2015).

Figure 4

Schematic Model Positing the Relationship between Tonic and Phasic Cortisol and Increased Alcohol Motivation and Intake. The solid line indicates the response to acute consumption in Low to Moderate Social Drinkers with less behavioral motivation and low self-administration of alcohol, whereas the dashed lines indicate high behavioral motivation and thus increased acute alcohol intake in Binge/Heavy and Chronic Drinkers. (a) A higher basal cortisol level is shown in Binge/Heavy and Chronic Drinkers relative to low-moderate, and (b) illustrates greater behavioral motivation and higher level of alcohol intake in Binge/Heavy and Chronic Drinkers with higher self-administered alcohol intake required to increase initial blunted cortisol responses towards more normal levels.

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Alcohol, stress, and glucocorticoids: From risk to dependence and relapse in alcohol use disorders - PubMed (original) (raw)