Anxiolytic- and antidepressant-like profile of a new CRF1 receptor antagonist, R278995/CRA0450

Chaki, Shigeyuki; Nakazato, Atsuro; Kennis, Ludo; Nakamura, Masato; Mackie, Claire; Sugiura, Masayuki; Vinken, Petra; Ashton, David; Langlois, Xavier; Steckler, Thomas

doi:10.1016/j.ejphar.2003.11.032

Cited by 127 publications

(112 citation statements)

References 45 publications

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…These results are consonant with those previously obtained in other tests sensitive to antidepressants (Griebel et al, 2002b, c). It is worth noting that another CRF1 receptor antagonist, R278995/CRA0450, has been recently reported to be inactive in the DRL-72 s schedule (Chaki et al, 2004). This apparent discrepancy between our result and those of Chaki and collaborators may be explained by the fact that, in addition to the antagonistic activity at the CRF1 receptor, R278995/ CRA0450 also showed a high affinity for the Sigma1 receptor.…”

Section: Discussionsupporting

confidence: 91%

Antidepressant-Like Effects of the Corticotropin-Releasing Factor 1 Receptor Antagonist, SSR125543, and the Vasopressin 1b Receptor Antagonist, SSR149415, in a DRL-72 s Schedule in the Rat

Louis

Cohen

Depoortère

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

The vasopressin 1b receptor antagonist, SSR149415, and the corticotropin-releasing factor 1 receptor antagonist, SSR125543, are orally active non-peptidic compounds with anxiolytic-and antidepressant-like activities in animal models. Presently, SSR149415 and SSR125543 were evaluated in a differential reinforcement of low-rate 72 s (DRL-72 s) schedule, a procedure known to respond differentially to antidepressants and anxiolytics. Male Wistar rats were trained to lever-press for food reinforcement, but only lever-presses occurring after a 72 s delay were reinforced; otherwise, presses were not rewarded, and the timer was reset to 0 s. The selective serotonin reuptake inhibitor, fluoxetine, and the benzodiazepine anxiolytic, diazepam, were tested in parallel. SSR149415 (10-30 mg/kg, i.p.) and SSR125543 (30 mg/kg, i.p.) increased the percentage of responses emitted in the inter-response time (IRT) bin (49-96 s), which resulted in a greater number of reinforced presses. Both compounds shifted the frequency distribution of responses toward longer IRT durations, with a preservation of the bell shape of the IRT distribution curve. Fluoxetine (10 mg/kg, i.p.) had an effect on DRL-72 s similar to that of SSR149415 and SSR125543. By contrast, diazepam increased the number of responses in IRT bin (0-12 s), and the IRT distribution curve was shifted toward shorter IRT durations and flattened. In summary, these results show that SSR149415 and SSR125543 displayed antidepressant-like activity in a DRL-72 s schedule in rat, confirming their therapeutic potential for the treatment of pathological states induced by chronic frustration such as depression.

show abstract

Section: Discussionsupporting

confidence: 91%

Antidepressant-Like Effects of the Corticotropin-Releasing Factor 1 Receptor Antagonist, SSR125543, and the Vasopressin 1b Receptor Antagonist, SSR149415, in a DRL-72 s Schedule in the Rat

Louis

Cohen

Depoortère

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…In comparison with CRFR2, CRFR1 exhibits a significantly higher affinity for CRF and shows far greater expression within the brain and in the pituitary (5,6). The dysregulation of the hypothalamic-pituitary-adrenal axis is thought to be involved in the onset of psychiatric diseases, such as depression, and specific CRFR1 antagonists have recently been shown to demonstrate anxiolytic-and antidepressant-like effects (7,8). GPCRs, like CRFR1, and their associated GPCR-interacting proteins (GIPs) have vast potential as pharmacological targets in the treatment of disease.…”

Section: Corticotropin-releasing Factor (Crf)mentioning

confidence: 99%

Role of SAP97 Protein in the Regulation of Corticotropin-releasing Factor Receptor 1 Endocytosis and Extracellular Signal-regulated Kinase 1/2 Signaling

Dunn

Walther

Godin

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: CRFR1 regulates the physiological response to stress and is implicated in the manifestation of depression. Results: SAP97 interacts and co-localizes with CRFR1, suppresses CRFR1 endocytosis, and is required for CRFR1-mediated ERK1/2 phosphorylation. Conclusion: SAP97 functionally regulates CRFR1 trafficking and signaling. Significance: This is the first documentation of functional regulation of CRFR1 by a specific PDZ protein.

show abstract

“…These findings suggest that CRF may be able to modulate DAergic neurotransmission throughout the rat mesolimbic system. For these reasons, the present study used a potent and selective CRF 1 receptor antagonist, CRA-0450 (Chaki et al, 2004), to examine the effects of acute versus chronic CRF 1 receptor blockade on mesencephalic DA neuron activity (determined by in vivo extracellular recordings) and DA overflow in the Acb (using in vivo microdialysis). In addition, the effect of CRF 1 receptor antagonism on cocaine-induced DA overflow in the Acb was examined and correlated with DA neuron activity in the VTA.…”

mentioning

confidence: 99%

Acute and Chronic Corticotropin-Releasing Factor 1 Receptor Blockade Inhibits Cocaine-Induced Dopamine Release: Correlation with Dopamine Neuron Activity

Lodge

Grace

2005

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Corticotropin-releasing factor (CRF) is a neuropeptide associated with the integration of the physiological and behavioral responses to stress. Recently, CRF 1 receptor antagonists have been shown to decrease cocaine self-administration and inhibit stress-induced reinstatement of cocaine-seeking behavior. The exact mechanisms underlying this effect are not clear. Based on the large amount of literature demonstrating an association between dopaminergic neurotransmission and reward-related behavior, the aim of the present study was to examine the effects of acute versus chronic CRF 1 receptor blockade on mesencephalic dopamine (DA) neuron activity (determined by in vivo extracellular recordings) and extracellular DA levels in the nucleus accumbens (Acb) (using in vivo microdialysis). In addition, the effect of CRF 1 receptor antagonism on cocaineinduced DA overflow in the Acb was examined and correlated with DA neuron activity in the ventral tegmental area (VTA).Acute (but not chronic) CRF 1 receptor blockade by CRA-0450 [1-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]-1,2,3,6-tetrahydropyridine-4-carboxamide benzenesulfonate] was found to significantly increase DA neuron population activity without affecting burst firing, average firing rate, or Acb DA levels. In addition, both acute and chronic CRF 1 receptor antagonism significantly reduced cocaine-stimulated DA overflow in the Acb, and this reduction was correlated with an attenuated cocaine-induced inhibition of DA population activity. Taken as a whole, these data demonstrate that, although DA neuron population activity exhibits tolerance to chronic CRF 1 receptor antagonism (by CRA-0450), tolerance does not develop to the selective inhibition of cocaine-induced DA release (in the Acb) and, as such, may be beneficial in the treatment of cocaine addiction.

show abstract

Anxiolytic- and antidepressant-like profile of a new CRF1 receptor antagonist, R278995/CRA0450

Cited by 127 publications

References 45 publications

Antidepressant-Like Effects of the Corticotropin-Releasing Factor 1 Receptor Antagonist, SSR125543, and the Vasopressin 1b Receptor Antagonist, SSR149415, in a DRL-72 s Schedule in the Rat

Antidepressant-Like Effects of the Corticotropin-Releasing Factor 1 Receptor Antagonist, SSR125543, and the Vasopressin 1b Receptor Antagonist, SSR149415, in a DRL-72 s Schedule in the Rat

Role of SAP97 Protein in the Regulation of Corticotropin-releasing Factor Receptor 1 Endocytosis and Extracellular Signal-regulated Kinase 1/2 Signaling

Acute and Chronic Corticotropin-Releasing Factor 1 Receptor Blockade Inhibits Cocaine-Induced Dopamine Release: Correlation with Dopamine Neuron Activity

Contact Info

Product

Resources

About