CRF1 Not Glucocorticoid Receptors Mediate Prepulse Inhibition Deficits in Mice Overexpressing CRF
| Autor: | Millan Mark, Marijke de Graaff, P. Monika Verdouw, Lucianne Groenink, Anneloes Dirks, Berend Olivier, Bernard W.M.M. Peeters |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Reflex Startle medicine.medical_specialty Genotype medicine.medical_treatment Neurophysiology Gene Expression Mice Transgenic Receptors Corticotropin-Releasing Hormone Mice chemistry.chemical_compound Hormone Antagonists Receptors Glucocorticoid Glucocorticoid receptor Corticosterone Internal medicine Animals Medicine Infusions Parenteral Benzodioxoles Receptor Biological Psychiatry Prepulse inhibition Depressive Disorder Major business.industry Adrenalectomy Mifepristone Disease Models Animal Steroid hormone Mitochondrial medicine [IGMD 8] Endocrinology Acoustic Stimulation Psychotic Disorders chemistry Steroids business hormones hormone substitutes and hormone antagonists Glucocorticoid medicine.drug |
| Zdroj: | Biological Psychiatry, 63, 4, pp. 360-368 Biological Psychiatry, 63, 360-368 |
| ISSN: | 0006-3223 |
| DOI: | 10.1016/j.biopsych.2007.06.002 |
| Popis: | Background Both 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. Methods Effects of the GR antagonists ORG34517 (5–45 mg/kg by mouth [PO]) and mifepristone (5–45 mg/kg PO) and the CRF 1 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). Results ORG34517 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 CRF 1 receptor antagonists, CP154,526 (40–80 mg/kg IP) and DMP695 (40 mg/kg IP), significantly restored PPI in CRF-overexpressing mice. Conclusions Sustained overactivation of CRF 1 receptors rather than excessive GR receptor stimulation underlies impaired sensorimotor gating in CRF-overexpressing mice. CRF 1 receptors thus may play a role in the expression of psychotic features in stress-related psychiatric disorders. |
| Databáze: | OpenAIRE |
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