Corticotropin-Releasing Factor 1 Antagonists Selectively Reduce Ethanol Self-Administration in Ethanol-Dependent Rats

Funk, Cindy K.; Zorrilla, Eric P.; Lee, Mei-Jing; Rice, Kenner C.; Koob, George F.

doi:10.1016/j.biopsych.2006.03.063

Cited by 262 publications

(270 citation statements)

References 94 publications

(148 reference statements)

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“…CRF 1 receptor antagonists can reduce levels of intake of postdependent animals to the levels observed in nondependent ones (54,58,59). Similarly, we found that 30 mg/kg CP-154,526 reduced the expression of the sensitized locomotor response to EtOH so that the level of activation was similar to that observed in mice that had received EtOH for the first time.…”

Section: Discussionsupporting

confidence: 75%

“…For various endocrine-independent effects of chronic EtOH, more profound effects of CRF 1 receptor manipulations have been described in postdependent animals and in animals that were selectively bred for elevated EtOH preference (54,58,59). CRF 1 receptor antagonists can reduce levels of intake of postdependent animals to the levels observed in nondependent ones (54,58,59).…”

Section: Discussionmentioning

confidence: 99%

“…Regarding alcoholism, human and rodent data support a genetically determined relationship between central CRF function and EtOH consumption (54)(55)(56)(57). EtOH-induced longterm neuroadaptations responsible for increased EtOH intake and stress-evoked relapse-like behavior in EtOH-dependent animals withdrawn from EtOH have also been linked to CRF function (54,58,59), and repeated EtOH exposure sensitizes the response to the activating effects of a central CRF administration (40). Together, these data provide convergent evidence that the neuroadaptive processes underlying chronic EtOH effects involve CRF neurotransmission.…”

Section: Deletion Of Ucn 1 Does Not Prevent Psychomotor Sensitizationmentioning

confidence: 95%

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Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: A urocortin ₁ -independent mechanism

Pastor

McKinnon

Scibelli

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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A common expression of neuroadaptations induced by repeated exposure to addictive drugs is a persistent sensitized behavioral response to their stimulant properties. Neuroplasticity underlying drug-induced sensitization has been proposed to explain compulsive drug pursuit and consumption characteristic of addiction. The hypothalamic-pituitary-adrenal (HPA) axis-activating neuropeptide, corticotropin-releasing factor (CRF), may be the keystone in drug-induced neuroadaptation. Corticosterone-activated glucocorticoid receptors (GRs) mediate the development of sensitization to ethanol (EtOH), implicating the HPA axis in this process. EtOHinduced increases in corticosterone require CRF activation of CRF1 receptors. We posited that CRF1 signaling pathways are crucial for EtOH-induced sensitization. We demonstrate that mice lacking CRF1 receptors do not show psychomotor sensitization to EtOH, a phenomenon that was also absent in CRF 1 ؉ 2 receptor doubleknockout mice. Deletion of CRF2 receptors alone did not prevent sensitization. A blunted endocrine response to EtOH was found only in the genotypes showing no sensitization. The CRF1 receptor antagonist CP-154,526 attenuated the acquisition and prevented the expression of EtOH-induced psychomotor sensitization. Because CRF1 receptors are also activated by urocortin-1 (Ucn1), we tested Ucn1 knockout mice for EtOH sensitization and found normal sensitization in this genotype. Finally, we show that the GR antagonist mifepristone does not block the expression of EtOH sensitization. CRF and CRF1 receptors, therefore, are involved in the neurobiological adaptations that underlie the development and expression of psychomotor sensitization to EtOH. A CRF/CRF1-mediated mechanism involving the HPA axis is proposed for acquisition, whereas an extrahypothalamic CRF/CRF1 participation is suggested for expression of sensitization to EtOH.addiction ͉ CP-154,526 ͉ HPA axis ͉ knockout mice ͉ psychomotor sensitization

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Deletion Of Ucn 1 Does Not Prevent Psychomotor Sensitizationmentioning

confidence: 95%

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Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: A urocortin ₁ -independent mechanism

Pastor

McKinnon

Scibelli

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Recently, studies also suggested distinct roles for the CRF 1 (vs the CRF 2 ) receptor pathway in ethanol dependence. In particular, during acute ethanol withdrawal, CRF 1 receptor activity was shown to mediate excessive ethanol self-administration in dependent animals, whereas activation of the CRF 2 receptor pathway reduced ethanol intake as well as anxiety-like behavior induced by ethanol withdrawal (Funk et al, 2007;Valdez et al, 2004). We have recently reported that genetic inactivation as well as pharmacological antagonism of the CRF 1 receptor pathway increased and prolonged the somatic expression of opiate withdrawal (Papaleo et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Disruption of the CRF2 Receptor Pathway Decreases the Somatic Expression of Opiate Withdrawal

Papaleo

Ghozland

Ingallinesi

et al. 2008

Neuropsychopharmacol

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Escape from the extremely aversive opiate withdrawal symptoms powerfully motivates compulsive drug-seeking and drug-taking behaviors. The corticotropin-releasing factor (CRF) system is hypothesized to mediate the motivational properties of drug dependence. CRF signaling is transmitted by two receptor pathways, termed CRF 1 and CRF 2 . To investigate the role for the CRF 2 receptor pathway in somatic opiate withdrawal, in the present study we used genetically engineered mice deficient in the CRF 2 receptor (CRF 2 À/À). We employed a novel, clinically relevant mouse model of 'spontaneous' opiate withdrawal as well as a classical opioid receptor antagonist (naloxone)-precipitated opiate withdrawal paradigm. To induce opiate dependence, mice were treated with intermittent escalating morphine doses (20-100 mg/kg, i.p.). We found that 8-128 h after the last opiate injection, CRF 2 À/À mice showed decreased levels of major somatic signs of spontaneous opiate withdrawal, such as paw tremor and wet dog shake, as compared to wild-type mice. Similarly, challenge with naloxone 2 h after the last morphine injection induced lower levels of paw tremor and wet dog shake in CRF 2 À/À mice as compared to wild-type mice. Despite the differences in somatic signs, wild-type and CRF 2 À/À mice displayed similar plasma corticosterone responses to opiate dosing and withdrawal, indicating a marginal role for the hypothalamus-pituitary-adrenal axis in the CRF 2 receptor mediation of opiate withdrawal. Our results unravel a novel role for the CRF 2 receptor pathway in opiate withdrawal. The CRF 2 receptor pathway might be a critical target of therapies aimed at alleviating opiate withdrawal symptoms and reducing relapse to drug intake.

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“…Rats with either a genetic predisposition for anxiety-like behavior and excessive drinking, or with a history of dependence, show decreases in drinking with administration of CRF 1 antagonists administered systemically (4,5). CRF antagonists also block stress-induced reinstatement to alcohol and other drugs of abuse (6).…”

Section: Financial Disclosuresmentioning

confidence: 99%

Alcoholism, Corticotropin-Releasing Factor, and Molecular Genetic Allostasis

Koob

2008

Biological Psychiatry

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Alcoholism, or Substance Dependence on alcohol, is a chronic relapsing disorder characterized by loss of control over intake (compulsive use) and the emergence of a negative emotional state during abstinence. Stress long has been considered a key element in the etiology of alcohol dependence, yet the exact mechanisms by which stress exacerbates and interacts with alcohol dependence have remained elusive. Recent work on the brain neurotransmitter corticotropinreleasing factor (CRF) [see footnote on nomenclature] has provided new insights into the stressalcohol dependence interaction. Two papers in this issue of Biological Psychiatry (1,2) provide an exciting molecular mechanism for this interaction that may have heuristic value for future translational advances.CRF is a 41 amino acid polypeptide with a wide distribution throughout the brain but high concentrations of cell bodies in the paraventricular nucleus of the hypothalamus, the basal forebrain (notably the amygdala and bed nucleus of the stria terminalis) and the brainstem. Central administration of CRF mimics the behavioral response to activation and stress in rodents, and administration of competitive CRF receptor antagonists generally have anti-stress effects (3). Two major CRF receptors have been identified, with CRF 1 receptor activation associated with increased stress responsiveness and CRF 2 receptor activation associated with decreases in feeding and decreased stress responsiveness, although there is some controversy in this area depending on the location of the CRF 2 receptors in question.In the current issue of Biological Psychiatry, Sommer et al. (1) studied rats using an animal model of alcohol dependence and showed that CRF and expression of the crh1 transcript within the amygdala are upregulated in postdependent animals. Animals trained to self-administer alcohol in a two-bottle, free-choice procedure and exposed to intermittent ethanol vapors to induce dependence showed a doubling of ethanol intake and increased sensitivity to stress which was reversed by a CRF receptor antagonist. CRF mRNA was increased in the central nucleus of the amygdala, and crh1 transcript expression was increased in the basolateral amygdala, with a concomitant decrease in crh2 transcript expression in the basolateral amygdala.These new results fit well with a burgeoning dataset implicating an increase in extrahypothalamic CRF function with the excessive drinking associated with alcohol

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Corticotropin-Releasing Factor 1 Antagonists Selectively Reduce Ethanol Self-Administration in Ethanol-Dependent Rats

Cited by 262 publications

References 94 publications

Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: A urocortin ₁ -independent mechanism

Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: A urocortin ₁ -independent mechanism

Disruption of the CRF2 Receptor Pathway Decreases the Somatic Expression of Opiate Withdrawal

Alcoholism, Corticotropin-Releasing Factor, and Molecular Genetic Allostasis

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Corticotropin-Releasing Factor 1 Antagonists Selectively Reduce Ethanol Self-Administration in Ethanol-Dependent Rats

Cited by 262 publications

References 94 publications

Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: A urocortin 1 -independent mechanism

Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: A urocortin 1 -independent mechanism

Disruption of the CRF2 Receptor Pathway Decreases the Somatic Expression of Opiate Withdrawal

Alcoholism, Corticotropin-Releasing Factor, and Molecular Genetic Allostasis

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Product

Resources

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Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: A urocortin ₁ -independent mechanism

Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: A urocortin ₁ -independent mechanism