Anti-sexual and anxiogenic behavioral consequences of corticotropin-releasing factor overexpression are centrally mediated

Heinrichs, Stephen C.; Min, Helen; Tamraz, Susan; Carmouché, Michelle; Boehme, Stefen A.; Vale, Wylie

doi:10.1016/s0306-4530(97)00030-9

Cited by 101 publications

(51 citation statements)

References 20 publications

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“…In addition to more classical pharmacological (Radulovic et al, 1999) and maternal deprivation experiments (Ladd et al, 1996;Eghbal-Ahmadi et al, 1997), recent evidence from transgenic mice strongly supports this hypothesis. For example, mice overexpressing CRF exhibit anxiogenic behaviors (Heinrichs et al, 1997), whereas those lacking the CRF 1 receptor exhibit decreased basal and stressinduced anxiety (Timpl et al, 1998). In contrast, animals lacking the CRF 2 receptor exhibit increased anxiety-like behavior and decreased stress-coping behaviors (Bale et al, 2000;Coste et al, 2000;Kishimoto et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Chronic Treatment with the Mood Stabilizers Valproic Acid and Lithium on Corticotropin-Releasing Factor Neuronal Systems

Gilmor¹,

Skelton²,

Nemeroff³

et al. 2003

J Pharmacol Exp Ther

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Corticotropin-releasing factor (CRF) plays a preeminent role in coordinating the endocrine, autonomic, and behavioral responses to stress. Dysregulation of both hypothalamic and extrahypothalamic CRF systems have been reported in patients with major depression and post-traumatic stress disorder. Moreover, effective treatment of these conditions leads to normalization of these CRF systems. Although there is virtually no data concerning alterations of CRF systems in bipolar disorder (manic depressive illness), previous work indicates that valproic acid, an anticonvulsant also effective in the treatment of acute mania, alters central CRF neuronal systems. In the current studies, we chronically administered valproic acid and lithium, two clinically effective mood stabilizers, in nonstressed rats to extend our previous findings. Chronic valproic acid administration decreased CRF mRNA expression in the paraventricular nucleus of the hypothalamus; lithium administration increased CRF mRNA expression in the central nucleus of the amygdala. Although valproic acid increased CRF 1 receptor mRNA expression in the cortex, CRF 1 receptor binding was decreased in both the basolateral amygdala and cortex, suggesting that chronic valproate treatment may in fact dampen the overall tone in this central stress pathway. Valproate treatment decreased CRF 2A mRNA expression in both the lateral septum and hypothalamus, although CRF 2A receptor binding was unchanged. Lithium administration decreased CRF 1 mRNA expression in both the amygdala and frontal cortex, but CRF 1 receptor binding also remained unchanged. These results suggest that the therapeutic actions of these mood stabilizers may, in part, result from their actions on central CRF neuronal systems. The distinct actions of each drug on CRF systems may underlie their synergistic clinical effects.

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Section: Discussionmentioning

confidence: 99%

The Effects of Chronic Treatment with the Mood Stabilizers Valproic Acid and Lithium on Corticotropin-Releasing Factor Neuronal Systems

Gilmor¹,

Skelton²,

Nemeroff³

et al. 2003

J Pharmacol Exp Ther

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“…These effects were potently blocked by administration of the CRH receptor antagonist α-helical CRH. CRH-Tg mice also showed a profound decrease in sexual behaviors and significant deficits in learning (Heinrichs et al, 1997).…”

Section: Crh Gene Targeting Micementioning

confidence: 97%

Site-specific overexpression of corticotropin-releasing hormone (CRH) in the mouse brain – modelling central CRH system hyperactivity

Steiner²,

Engelholm³

et al. 2005

Pharmacopsychiatry

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“…Os modelos de ratos transgênicos produtores de quantidades anormalmente elevadas de CRH têm sido de utilidade no estudo sistemático dos efeitos da exposição crônica a grandes quantidades deste peptídeo. Estes animais mostram-se ansiosos durante períodos de estresse e desenvolvem síndrome de Cushing (20,21) enquanto que os ratos que carecem do rCRH-1 ( knockouts ) mostram-se menos ansiosos (22). Em contrapartida, baseado em achados no modelo knockoutdo rCRH-2 no camundongo, especula-se que a ativação deste receptor resulte em efeitos ansiolíticos, embora tais observações tenham sido refutadas por alguns pesquisadores.…”

Section: Receptores Do Crhunclassified

Antagonistas do hormônio liberador da corticotrofina: atualização e perspectivas

Ayala¹

2002

Arq Bras Endocrinol Metab

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RESUMOModelos genéticos e estudos epidemiológicos têm contribuído para a compreensão da fisiopatologia das doenças relacionadas ao estresse. O hormônio liberador da corticotrofina (CRH) pertence à família dos chamados peptídeos relacionados ao CRH, junto com a urocortina, urocortina II (ou peptídeo relacionado à estressecopina) e urocortina III (ou estressecopina). O CRH é o maior estimulador da secreção hipofisária de ACTH em humanos, e tem um papel importante na resposta fisiológica ao estresse. O CRH e seus receptores (tipos 1 e 2) estão difusamente distribuí -dos em todo o sistema nervoso central (SNC) e, em menor proporção, em tecidos periféricos. A distribuição dos receptores no SNC mostra ampla variabilidade entre as espécies. Os neurônios do CRH modulam a função autonômica e do sistema límbico. O CRH tem importantes efeitos, também, nos sistemas cardiovascular, metabólico e comportamental. As ações regionais deste peptídeo no SNC e na periferia são vários e apenas parcialmente conhecidos. Ações aberrantes do CRH estão implicadas em algumas condições psiquiátricas, incluindo depressão e ansiedade. Esta teoria tem sido corroborada por dados em ratos transgênicos que não expressam CRH e estudos pré-clínicos envolvendo a administração de antagonistas do CRH em macacos Rhesus. Embora ainda não disponível para uso clínico de rotina, dados preliminares de estudos conceituais envolvendo a administração oral de antagonistas do CRH em humanos são encorajadores. Entretanto, ainda permanece um desafio o desenvolvimento de antagonistas não peptídicos seletivos do receptor de CRH. Além disso, são extremamente necessários testes com estudos clíni -cos randomizados, que deverão trazer novas luzes sobre esta área. Genetic models and epidemiological studies have contributed to our understanding of the pathophysiology of stress-related disorders. Corticotropin-releasing hormone (CRH) belongs to the family of the so-called CRH related peptides along with Urocortin, Urocortin II (or Stresscopin Related Peptide) and Urocortin III (or Stresscopin). CRH is the major stimulus for pituitary ACTH secretion in humans and plays a major role in the physiologic response to stress. CRH and its receptors (type 1 and 2) are widely distributed throughout the central nervous system and to a lesser extent in peripheral tissues. The receptor distribution in the CNS exhibits a wide inter-species variability. The CRH neurons modulate autonomic and limbic system function. CRH affects a wide array of cardiovascular, metabolic and behavioral effects. The regional actions of this peptide in the CNS and in the periphery are varied and only partially understood. Aberrant CRH action is implicated in psychiatric disorders including depression and anxiety. Data from transgenic mice lacking over expressing CRH and pre-clinical studies involving CRH antagonist administration to Rhesus monkeys have substantiated this theory.Although not yet available for routine clinical use, preliminary proofs of concept studies revisão

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Anti-sexual and anxiogenic behavioral consequences of corticotropin-releasing factor overexpression are centrally mediated

Cited by 101 publications

References 20 publications

The Effects of Chronic Treatment with the Mood Stabilizers Valproic Acid and Lithium on Corticotropin-Releasing Factor Neuronal Systems

The Effects of Chronic Treatment with the Mood Stabilizers Valproic Acid and Lithium on Corticotropin-Releasing Factor Neuronal Systems

Site-specific overexpression of corticotropin-releasing hormone (CRH) in the mouse brain – modelling central CRH system hyperactivity

Antagonistas do hormônio liberador da corticotrofina: atualização e perspectivas

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