Upregulation of Voluntary Alcohol Intake, Behavioral Sensitivity to Stress, and Amygdala Crhr1 Expression Following a History of Dependence

Sommer, Wolfgang; Rimondini, Roberto; Hansson, Anita C.; Hipskind, Philip A.; Gehlert, Donald R.; Barr, Christina S.; Heilig, Markus

doi:10.1016/j.biopsych.2007.01.010

Cited by 295 publications

(376 citation statements)

References 52 publications

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“…2 [6,23]. As predicted from the allostatic concept of addiction (Box 1) we found upregulated CRH activity in the central amygdala of postdependent animals during acute withdrawal and many weeks thereafter, contributing to increased ethanol intake, anxiety, and ethanol-seeking behavior, all of which can be alleviated by blockade of CRH 1 receptors [6,[23][24][25][26]. In fact, the excessive ethanol consumption appears to be a means to downregulate amygdala CRH 1 receptors [27].…”

Section: Introductionsupporting

confidence: 52%

“…1), in close proximity to the locus of highest extrahypothalamic Crh mRNA expression. Interestingly, CRH 1 receptors appear upregulated in the medial amygdala during states of increased behavioral sensitivity to stress [6]. However, most of the cellular and molecular interactions between these systems are still unknown.…”

Section: Introductionmentioning

confidence: 99%

“…The hallmarks of the resulting behavioral syndrome, collectively labeled as the postdependent state, are excessive ethanol consumption and increased behavioral sensitivity to stress that persist long beyond acute withdrawal ( Fig. 2 [6,23]. As predicted from the allostatic concept of addiction (Box 1) we found upregulated CRH activity in the central amygdala of postdependent animals during acute withdrawal and many weeks thereafter, contributing to increased ethanol intake, anxiety, and ethanol-seeking behavior, all of which can be alleviated by blockade of CRH 1 receptors [6,[23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

“…In summary, inhibition of the CRH 1 receptor subtype has been proposed as an attractive target for medication development in anxiety, depression, and addiction [23,30,31] and promising compounds are in development [6,25,32]. On the other hand, a wide variety of safe and effective RAS-targeting medications exist, but their potential as adjuvant medications for these disorders is largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

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Targeting brain angiotensin and corticotrophin-releasing hormone systems interaction for the treatment of mood and alcohol use disorders

Sommer

Saavedra

2008

J Mol Med

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The brain renin-angiotensin system (RAS) participates importantly in the regulation of endocrine, autonomic, and behavioral response to stress. Recent data indicate that central action of AT 1 receptor antagonists can reduce anxiety symptoms in experimental animals. Furthermore, central inhibition of RAS activity decreases ethanol intake in an animal model of alcoholism. Pathological anxiety responses and the development of substance dependence are both critically mediated through corticotrophin-releasing hormone (CRH) systems, and the RAS is positioned to interact both with hypothalamic as well as extrahypothalamic CRH systems. The thesis of this paper is that the RAS is part of the neurochemical dysregulation underlying negative affective states, anxiety disorders, and ethanol dependence and that medications targeting the RAS should be considered to augment the treatment of these disorders.

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Section: Introductionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Targeting brain angiotensin and corticotrophin-releasing hormone systems interaction for the treatment of mood and alcohol use disorders

Sommer

Saavedra

2008

J Mol Med

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“…Second, studies have also implicated CRHR1 SNPs in heavy alcohol use during adolescence (Blomeyer et al, 2008) and binge drinking (Treutlein et al, 2006), and CRHR1 gene upregulation has been linked to the risk of relapse after cessation of drinking (Sommer et al, 2008). CRHR1 SNPs also interact with stressful life events to predict heavy drinking among 19-year-olds (Schmid et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

FKBP5 and CRHR1 polymorphisms moderate the stress–physical health association in a national sample.

Lessard¹,

Holman²

2014

Health Psychology

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Objective: Stressful life events experienced during childhood and as an adult negatively impact mental and physical health over the life span. This study examined polymorphisms from 2 hypothalamicpituitary-adrenal axis-related genes previously associated with posttraumatic stress disorder-FKBP5 and CRHR1-as moderators of the impact of child abuse and adult stress on physical health. Method: A national, community-based subsample of non-Hispanic European American respondents (n ϭ 527) from a prospective longitudinal 3-year study of stress and coping (N ϭ 2,729) provided saliva for genotyping. Results: FKBP5 (rs1360780) and CRHR1 (rs12944712) polymorphisms significantly interacted with child abuse and adult stress to predict increases in physical health ailments over 3 years. Child abuse and adult stress were strongly related to physician-diagnosed physical ailments among individuals with the risk alleles of both single nucleotide polymorphisms. Individuals carrying the low-risk homozygotic genotypes were protected from the long-term negative health implications of experiencing both child abuse and adult stress. Conclusion: Consistent with theories linking the hypothalamic-pituitary-adrenal axis with stress-related disease, hypothalamic-pituitary-adrenal axis polymorphism genotypes moderated the association between exposure to child abuse/adult stress and long-term physical health outcomes in a national sample.

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Neurobiology of Stress and Drug Use Vulnerability in Culturally Diverse Communities

Obasi¹,

Wilborn²,

Cavanagh³

et al. 2017

The Handbook of Culture and Biology

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Upregulation of Voluntary Alcohol Intake, Behavioral Sensitivity to Stress, and Amygdala Crhr1 Expression Following a History of Dependence

Cited by 295 publications

References 52 publications

Targeting brain angiotensin and corticotrophin-releasing hormone systems interaction for the treatment of mood and alcohol use disorders

Targeting brain angiotensin and corticotrophin-releasing hormone systems interaction for the treatment of mood and alcohol use disorders

FKBP5 and CRHR1 polymorphisms moderate the stress–physical health association in a national sample.

Neurobiology of Stress and Drug Use Vulnerability in Culturally Diverse Communities

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