Reduced anxiety-like and cognitive performance in mice lacking the corticotropin-releasing factor receptor 11Published on the World Wide Web on 27 November 1998.1

Contarino, Angelo; Dellu, F.; Koob, George F.; Smith, George W.; Lee, Kuo Fen; Vale, Wylie; Gold, Lisa

doi:10.1016/s0006-8993(98)01158-5

Cited by 219 publications

(90 citation statements)

References 45 publications

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“…The elevated plus maze (EPM) apparatus and experimental conditions were as previously described. 40 The time spent on the open arms was expressed as a percentage of the total test duration. The number of entries into the open arms, and the number of total entries to both open and closed arms were scored.…”

Section: Animalsmentioning

confidence: 99%

Urocortin-1 and -2 double-deficient mice show robust anxiolytic phenotype and modified serotonergic activity in anxiety circuits

et al. 2009

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The urocortin (Ucn) family of neuropeptides is suggested to be involved in homeostatic coping mechanisms of the central stress response through the activation of corticotropin-releasing factor receptor type 2 (CRFR2). The neuropeptides, Ucn1 and Ucn2, serve as endogenous ligands for the CRFR2, which is highly expressed by the dorsal raphe serotonergic neurons and is suggested to be involved in regulating major component of the central stress response. Here, we describe genetically modified mice in which both Ucn1 and Ucn2 are developmentally deleted. The double knockout mice showed a robust anxiolytic phenotype and altered hypothalamic-pituitary-adrenal axis activity compared with wild-type mice. The significant reduction in anxiety-like behavior observed in these mice was further enhanced after exposure to acute stress, and was correlated with the levels of serotonin and 5-hydroxyindoleacetic acid measured in brain regions associated with anxiety circuits. Thus, we propose that the Ucn/ CRFR2 serotonergic system has an important role in regulating homeostatic equilibrium under challenge conditions.

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Section: Animalsmentioning

confidence: 99%

Urocortin-1 and -2 double-deficient mice show robust anxiolytic phenotype and modified serotonergic activity in anxiety circuits

et al. 2009

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“…Surprisingly, during behavioral testing we found that the male CRFR1-mutant mice did not display the characteristic robust anxiolytic-like behavior reported for these mice (Smith et al, 1998;Timpl et al, 1998;Contarino et al, 1999). By examining differences in breeding schemes, we have found a significant correlation between the genotype of the dam and the anxiety-like behavior detected in the male mice.…”

Section: Discussionmentioning

confidence: 70%

Mice Deficient for Both Corticotropin-Releasing Factor Receptor 1 (CRFR1) and CRFR2 Have an Impaired Stress Response and Display Sexually Dichotomous Anxiety-Like Behavior

et al. 2002

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Corticotropin-releasing factor (CRF) and its family of peptides are critical coordinators of homeostasis whose actions are mediated through their receptors, CRF receptor 1 (CRFR1) and CRFR2, found throughout the CNS and periphery. The phenotypes of mice deficient in either CRFR1 or CRFR2 demonstrate the critical role these receptors play. CRFR1-mutant mice have an impaired stress response and display decreased anxiety-like behavior, whereas CRFR2-mutant mice are hypersensitive to stress and display increased anxiety-like behavior. To further elucidate the roles of both CRF receptors and determine their interaction in behaviors, we have generated mice deficient in both CRFR1 and CRFR2. The behavioral phenotype of these mice demonstrates a novel role of the mother's genotype on development of pup anxiety. We have found that although the female double-mutant mice display anxiolytic-like behavior, the male double-mutant mice show significantly more anxiety-like behavior compared with the females. We have also determined that the dam's CRFR2 genotype affects the anxiety-like behavior of the male mice, such that a pup born to a heterozygous or mutant dam displays significantly more anxiety-like behavior regardless of that pup's genotype. Double-mutant mice also display an even greater impairment of their hypothalamic-pituitary-adrenal axis response to stress than that of the CRFR1-mutant mice. CRF mRNA levels are elevated in CRFR1-and double-mutant mice, and urocortin III and vasopressin mRNA levels are increased in CRFR2-and double-mutant mice. These results indicate that both CRFR1 and CRFR2 have critical roles in gene regulation and the maintenance of homeostasis in response to stress.

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“…In particular, either CRF 1 receptor deficiency or functional antagonism of the CRF 1 receptor pathway decreased anxiety-like and depressionlike behavior (Contarino et al, 1999;Griebel et al, 2002;Hodgson et al, 2007;Nielsen et al, 2004;Okuyama et al, 1999;Smith et al, 1998;Timpl et al, 1998;Zorrilla et al, 2002). Also, CRF 1 À/À mice displayed deficient HPA axis responses to stressful events (Contarino and Papaleo, 2005;Papaleo et al, 2007;Smith et al, 1998;Timpl et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Genetically engineered mouse models have allowed the discovery of distinct and often opposite functions for the two known CRF receptor pathways (Bale and Vale, 2004;Contarino and Gold, 2002). In particular, CRF 1 receptordeficient mice display decreased hypothalamus-pituitaryadrenal (HPA) axis as well as behavioral reactions to stressors (Contarino et al, 1999;Muller et al, 2003;Smith et al, 1998;Timpl et al, 1998). In net contrast, CRF 2 receptor-deficient mice show increased HPA axis and affective-like responses to stressors (Bale et al, 2000;Bale and Vale, 2003;Coste et al, 2000Coste et al, , 2006Kishimoto et al, 2000).…”

Section: Introductionmentioning

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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Reduced anxiety-like and cognitive performance in mice lacking the corticotropin-releasing factor receptor 11Published on the World Wide Web on 27 November 1998.1

Cited by 219 publications

References 45 publications

Urocortin-1 and -2 double-deficient mice show robust anxiolytic phenotype and modified serotonergic activity in anxiety circuits

Urocortin-1 and -2 double-deficient mice show robust anxiolytic phenotype and modified serotonergic activity in anxiety circuits

Mice Deficient for Both Corticotropin-Releasing Factor Receptor 1 (CRFR1) and CRFR2 Have an Impaired Stress Response and Display Sexually Dichotomous Anxiety-Like Behavior

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

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