Corticotropin-releasing hormone and dopamine release in healthy individuals. (February 2017)

• Record Type: Journal Article
• Authors: Payer, Doris; Williams, Belinda; Mansouri, Esmaeil; Stevanovski, Suzanna; Nakajima, Shinichiro; Le Foll, Bernard; Kish, Stephen; Houle, Sylvain; Mizrahi, Romina; George, Susan R.; George, Tony P.; Boileau, Isabelle
• Is Part Of: Psychoneuroendocrinology. Volume 76(2017)
• Page Start: 192
• Page End: 196
• Publication Date: 2017-02
• Subjects: Corticotropin-releasing hormone (CRH) -- Dopamine (DA) -- Positron emission tomography (PET) -- [11C]-(+)-PHNO -- Stress-induced relapse -- Addiction; Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2016.11.034
• Languages: English
• ISSNs: 0306-4530

Abstract

Highlights: We investigated dopamine release in striatum, midbrain and pallidum after injection of human corticotropin hormone (i.v.) in humans. Two positron emission tomography scans with the dopamine D2/3 receptor agonist [11C]-(+)-PHNO were conducted: one after placebo and one after iv corticotropin hormone. We report that iv corticotropin hormone led to a detectable decrease in overall [11C]-(+)-PHNO binding, interpreted as increased dopamine release. Abstract: Corticotropin-releasing hormone (CRH) is a key component of the neuroendocrine response to stress. In animal models, CRH has been shown to modulate dopamine release, and this interaction is believed to contribute to stress-induced relapse in neuropsychiatric disorders. Here we investigated whether CRH administration induces dopamine release in humans, using positron emission tomography (PET). Eight healthy volunteers (5 female, 22–48 years old) completed two PET scans with the dopamine D2/3 receptor radioligand [ 11 C]-(+)-PHNO: once after saline injection, and once after injection of corticorelin (synthetic human CRH). We also assessed subjective reports and measured plasma levels of endocrine hormones (adrenocorticotropic hormone and cortisol). Relative to saline, corticorelin administration decreased binding of the D2/3 PET probe [ 11 C]-(+)-PHNO, suggesting dopamine release. Endocrine stress markers were also elevated, in line with activation of the hypothalamic-pituitary-adrenal axis, but we detected no changes in subjective ratings. Preliminary results from this proof-of-concept study suggests that CRH challenge in combination with [ 11 C]-(+)-PHNO PET may serve as an assay of dopamine release, presenting a potential platform for evaluating CRH/dopamine interactions in neuropsychiatric disorders and CRH antagonists as potential treatment avenues.