کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4180108 1276587 2008 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
CRF1 Not Glucocorticoid Receptors Mediate Prepulse Inhibition Deficits in Mice Overexpressing CRF
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
CRF1 Not Glucocorticoid Receptors Mediate Prepulse Inhibition Deficits in Mice Overexpressing CRF
چکیده انگلیسی

BackgroundBoth corticotropin-releasing factor (CRF) and glucocorticoid receptors (GR) are implicated in the psychotic symptoms of psychiatric disorders. Correspondingly, it is of interest to determine their respective involvement in the sensorimotor gating deficits displayed by transgenic mice overexpressing CRF. These mice reveal lifelong elevations of CRF and corticosterone levels.MethodsEffects of the GR antagonists ORG34517 (5–45 mg/kg by mouth [PO]) and mifepristone (5–45 mg/kg PO) and the CRF1 receptor antagonists CP154,526 (20–80 mg/kg intraperitoneally [IP]) and DMP695 (2.5–40.0 mg/kg IP) on prepulse inhibition (PPI) of the acoustic startle response were studied in mice overexpressing CRF and in their wild-type littermates. In addition, PPI was measured in both genotypes 2 weeks after adrenalectomy with or without exogenous corticosterone administration via subcutaneous pellet implant (20 mg corticosterone).ResultsORG34517 and mifepristone did not influence perturbation of PPI in mice overexpressing CRF; reducing corticosterone levels by adrenalectomy likewise did not improve PPI. Further, elevation in corticosterone levels by pellet implantation did not disrupt PPI in wild-type mice. Conversely, both CRF1 receptor antagonists, CP154,526 (40–80 mg/kg IP) and DMP695 (40 mg/kg IP), significantly restored PPI in CRF-overexpressing mice.ConclusionsSustained overactivation of CRF1 receptors rather than excessive GR receptor stimulation underlies impaired sensorimotor gating in CRF-overexpressing mice. CRF1 receptors thus may play a role in the expression of psychotic features in stress-related psychiatric disorders.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biological Psychiatry - Volume 63, Issue 4, 15 February 2008, Pages 360–368
نویسندگان
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