Abstract:
RATIONALE:Exposure to extreme stress has been suggested to produce long-term, detrimental alterations in the hypothalamic-pituitary-adrenal (HPA) axis leading to the development of mental disorders such as depression. Therefore, compounds that block the effects of stress hormones were investigated as potential therapeutics for depression. OBJECTIVES:In the present study, we compared the potential antidepressant-like effects of four CRF antagonists, antalarmin, CP154,526, R121919, and LWH234 (at 3, 10, and 30 mg/kg i.p., 60 min prior to the forced swim test) and the corresponding effect on swim-induced HPA activation to better elucidate the relation between HPA activity and antidepressant activity. METHODS:The antidepressant-like effects of the CRF antagonists and known antidepressants were determined in the rat forced swim test, and blood samples were obtained before and after swimming for the evaluation of adrenocorticotropin-releasing hormone (ACTH) levels. RESULTS:Antalarmin, CP154,526, and R121919 did not produce antidepressant-like effects in the forced swim test although these compounds decreased swim-induced increases in ACTH to various extents. In contrast, LWH234 reduced immobility in the forced swim test, without altering the swim-stress-induced ACTH response. However, this compound antagonized restraint-induced ACTH release. CONCLUSIONS:These data suggest that reducing stress-induced increases in HPA activity alone may not be sufficient to produce antidepressant-like activity; however, reductions in HPA activity may contribute to antidepressant actions of some treatments. In addition, it is proposed that CRF antagonists may alter differentially the HPA axis depending on the type of stressor used or behavioral measure evaluated.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Jutkiewicz EM,Wood SK,Houshyar H,Hsin LW,Rice KC,Woods JHdoi
10.1007/s00213-005-2164-zsubject
Has Abstractpub_date
2005-07-01 00:00:00pages
215-23issue
2eissn
0033-3158issn
1432-2072journal_volume
180pub_type
杂志文章abstract::NCQ 298 ((S)-3-iodo-N-[(l-ethyl-2-pyrrolidinyl)methyl]-5,6- dimethoxysalicylamide) has an iodine substituent. We have labelled NCQ 298 with 123I and 125I, and used the radioligands as tracers in receptor studies in vitro, in vivo in autoradiography and in SPECT studies on Cynomolgus monkeys. [125I]NCQ 298 bound in vit...
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pub_type: 杂志文章
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pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 杂志文章,随机对照试验
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journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Psychopharmacology
pub_type: 杂志文章
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abstract::Oxytocin plays an important role in the regulation of normal cognitive functions and behaviors, which are disturbed in schizophrenia. Several studies suggest that oxytocinergic function is abnormal in schizophrenia patients. Thus, oxytocin may be involved in the pathophysiology associated with this disorder. This stud...
journal_title:Psychopharmacology
pub_type: 杂志文章
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更新日期:1999-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
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更新日期:2008-09-01 00:00:00