Chronic infusion of a CRH1 receptor antisense oligodeoxynucleotide into the central nucleus of the amygdala reduced anxiety-related behavior in socially defeated rats

Liebsch, Gudrun; Landgraf, Rainer; Gerstberger, R.; Probst, Joseph Christopher; Wotjak, Carsten T.; Engelmann, Mario; Holsboer, Florian; Montkowski, Alexandra

doi:10.1016/0167-0115(95)00099-w

Cited by 216 publications

(124 citation statements)

References 37 publications

Supporting

Mentioning

116

Contrasting

Unclassified

Order By: Relevance

“…It is important to emphasize however, that the two studies differ in primary cohort (bipolar vs unipolar) and brain region of interest (anterior cingulated/medial prefrontal cortex vs occipital lobe). Nonetheless, recent preclincal data have highlighted that CRF1 receptors (activation associated with anxiogenic behavior; Liebsch et al, 1995) and CRF2 receptors (activation involved in stress mediated coping behavior; Liebsch et al, 1999) differentially regulate glutamate transmission (Liu et al, 2004). In the central nucleus of the amygdala, CRF decreased glutamatergic transmission through a CRF1 mediated post-synaptic action; conversely, in the lateral septum mediolateral nucleus, CRF caused a CRF1 mediated facilitation of glutamatergic transmission.…”

Section: Discussionmentioning

confidence: 99%

Increased Anterior Cingulate/Medial Prefrontal Cortical Glutamate and Creatine in Bipolar Depression

Frye

Watzl

Banakar

et al. 2007

Neuropsychopharmacol

202

127

View full text Add to dashboard Cite

Proton magnetic resonance spectroscopy ( 1 HMRS) is an in vivo brain imaging method that can be used to investigate psychotropic drug mechanism of action. This study evaluated baseline 1 HMRS spectra of bipolar depressed patients and whether the level of cerebral metabolites changed after an open trial of lamotrigine, an anti-glutamatergic mood stabilizer. Twenty-three bipolar depressed and 12 control subjects underwent a MRS scan of the anterior cingulate/medial prefrontal cortex. The scan was performed on a GE whole-body 1.5 T MRI scanner using single-voxel PRESS (TE/TR ¼ 30/3000 ms, 3 Â 3 Â 3 cm 3 and post-processed offline with LCModel. Baseline CSF-corrected absolute concentrations of glutamate + glutamine ([Glx]), glutamate ([Glu]), and creatine + phosphocreatine ([Cr]) were significantly higher in bipolar depressed subjects vs healthy controls. The non-melancholic subtype had significantly higher baseline [Glx] and [Glu] levels than the melancholic subtype. Remission with lamotrigine was associated with significantly lower post-treatment glutamine ([Gln]) in comparison to non-remission. These data suggest that non-melancholic bipolar depression is characterized by increased glutamate coupled with increased energy expenditure. Lamotrigine appears to reduce glutamine levels associated with treatment remission. Further study is encouraged to determine if these MR spectroscopic markers can delineate drug mechanism of action and subsequent treatment response.

show abstract

Section: Discussionmentioning

confidence: 99%

Increased Anterior Cingulate/Medial Prefrontal Cortical Glutamate and Creatine in Bipolar Depression

Frye

Watzl

Banakar

et al. 2007

Neuropsychopharmacol

202

127

View full text Add to dashboard Cite

show abstract

“…This could be demonstrated in several animal studies. Central subchronic administration of anti-CRF 1 receptor oligodeoxynucleotides in rats and mice produced anxiolytic effects (Heinrichs et al, 1997;Liebsch et al, 1995Liebsch et al, , 1999Skutella et al, 1998) but did not alter plasma ACTH and corticosterone concentrations (Heinrichs et al, 1997;Liebsch et al, 1999). Muller et al (2003) examined anxiety related behavior in conditional CRF 1 knockout mice with CRF 1 receptor function postnatally inactivated in anterior forebrain and limbic structures but not in the pituitary.…”

Section: Discussionmentioning

confidence: 99%

High-Affinity CRF1 Receptor Antagonist NBI-34041: Preclinical and Clinical Data Suggest Safety and Efficacy in Attenuating Elevated Stress Response

Ising

Zimmermann

Kuenzel

et al. 2007

Neuropsychopharmacol

Self Cite

133

101

View full text Add to dashboard Cite

There is an extensive evidence that corticotropin releasing factor (CRF) is hypersecreted in depression and anxiety, and blockade of CRF could have therapeutic benefit. We report preclinical data and the results of a clinical Phase I study with the novel nonpeptide CRF 1 antagonist NBI-34041/SB723620. Preclinical data conducted with different cell lines expressing human CRF receptors and in Wistar and Sprague-Dawley rats indicate that NBI-34041 is effective in reducing endocrine responses to pharmacological and behavioral challenge mediated by CRF 1 receptors. These specific properties and its well-documented safety profile enabled a clinical Phase I study with 24 healthy male subjects receiving NBI-34041 (10, 50, or 100 mg) or placebo for 14 days. Regulation of the hypothalamic-pituitaryadrenocortical (HPA) axis was evaluated by intravenous stimulation with 100 mg of human CRF. Psychosocial stress response was investigated with the Trier Social Stress Test (TSST). Treatment with NBI-34041 did not impair diurnal adrenocorticotropic hormone (ACTH) and cortisol secretion or CRF evoked ACTH and cortisol responses but attenuated the neuroendocrine response to psychosocial stress. These results suggest that NBI-34041 is safe and does not impair basal regulation of the HPA system but improves resistance against psychosocial stress. NBI-34041 demonstrates that inhibition of the CRF system is a promising target for drug development against depression and anxiety disorders.

show abstract

“…If CRH is absent, other neuropeptides such as urocortin or other yet-to-be identified molecules acting at CRH1 or CRH2 receptors (and possibly CRH receptors yet-to-be discovered) can serve as anxiogenic or depressogenic signals (Weninger et al 1999). Studies by Liebsch et al (1995Liebsch et al ( , 1999, Heinrichs et al (1997), and Skutella et al (1998), who used antisense probes directed against the mRNA-encoding CRH-R1 and CRH-R2 in rats, and also studies involving mouse mutants lacking CRH-R1, suggested that CRH-R1 mediates anxiety-like behavior (Timpl et al 1998;Smith et al 1998) (Figure 2). In contrast, CRH-R2 deficiency was shown to increase anxiety-like behavior in some (Bale et al 2000;Kishimoto et al 2000) but not all (Coste et al 2000) studies, raising the possibility that the two so far identified CRH receptors mediate opposite effects on anxiety-like behavior.…”

Section: Knock-out or Transgenic Manipulation Of Crh And Corticosteromentioning

confidence: 99%

The Corticosteroid Receptor Hypothesis of Depression

Holsboer

2000

Neuropsychopharmacology

1,978

1,228

View full text Add to dashboard Cite

Clinical EvidenceUntil now, the serendipitous discovery of antidepressants in the 1950s has profoundly inspired hypotheses of the pathogenesis of depression. The well-known pharmacological effects of antidepressants on presynaptic uptake transporters and degradating enzymes (i.e., MAO) of serotonin and norepinephrine has focused research on causality and treatment of depression on the metabolism of functional biogenic amines and the capacity of their respective receptors to alter intracellular signaling pathways that ultimately induce changes in gene activity. Elevated circulating levels of stress hormones among depressives were recognized even before antidepressants were discovered, but these changes were seen as epiphenomena, reflecting the stressful experience of depression, although M. Bleuler (1919) already demonstrated that hormones have diverse psychotropic effects and suggested hormone treatments as potential antidepressants. A vast amount of evidence has accumulated, that reject the view that altered stress hormone secretions in depression are epiphenomenal. During the past decade, several research groups formulated a hypothesis relating aberrant stress hormone dysregulation to causality of depression and submitted that antidepressants may act through normalisation of these HPA changes (

show abstract

Chronic infusion of a CRH1 receptor antisense oligodeoxynucleotide into the central nucleus of the amygdala reduced anxiety-related behavior in socially defeated rats

Cited by 216 publications

References 37 publications

Increased Anterior Cingulate/Medial Prefrontal Cortical Glutamate and Creatine in Bipolar Depression

Increased Anterior Cingulate/Medial Prefrontal Cortical Glutamate and Creatine in Bipolar Depression

High-Affinity CRF1 Receptor Antagonist NBI-34041: Preclinical and Clinical Data Suggest Safety and Efficacy in Attenuating Elevated Stress Response

The Corticosteroid Receptor Hypothesis of Depression

Contact Info

Product

Resources

About