title: Corticotropin-releasing hormone and dopamine release in healthy individuals.
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 D2/3receptor radioligand [11C]-(+)-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 D2/3PET probe [11C]-(+)-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 [11C]-(+)-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.
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, Canada; Addictions Division, Centre for Addiction and Mental Health, 100 Stokes St., Toronto, ON, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, 250 College St., Toronto, ON, Canada.
authors.forename: Doris
authors.initials: D
authors.lastname: Payer
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, Canada.
authors.forename: Belinda
authors.initials: B
authors.lastname: Williams
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, Canada.
authors.forename: Esmaeil
authors.initials: E
authors.lastname: Mansouri
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, Canada.
authors.forename: Suzanna
authors.initials: S
authors.lastname: Stevanovski
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, Canada.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, 250 College St., Toronto, ON, Canada; Departments of Medicine, Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Foll
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, 250 College St., Toronto, ON, Canada; Departments of Medicine, Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kish
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, 250 College St., Toronto, ON, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, 250 College St., Toronto, ON, Canada.
authors.forename: Romina
authors.initials: R
authors.lastname: Mizrahi
authors.affiliation: Departments of Medicine, Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON, Canada.
authors.forename: Susan R
authors.initials: SR
authors.lastname: George
authors.affiliation: Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, 250 College St., Toronto, ON, Canada; Schizophrenia Division, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, Canada.
authors.forename: Tony P
authors.initials: TP
authors.lastname: George
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, 250 College St., Toronto, ON, Canada. Electronic address: Isabelle.Boileau@camh.ca.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boileau
mesh_terms: D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000378:metabolism; D005260:Female; D005917:Globus Pallidus / Q000000981:diagnostic imaging / Q000378:metabolism*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000000981:diagnostic imaging / Q000378:metabolism*; D008875:Middle Aged; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D010078:Oxazines / Q000378:metabolism; D049268:Positron-Emission Tomography; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D010078:Oxazines; C042631:naxagolide; D003346:Corticotropin-Releasing Hormone; D004298:Dopamine
keywords: Addiction; Corticotropin-releasing hormone (CRH); Dopamine (DA); Positron emission tomography (PET); Stress-induced relapse; [(11)C]-(+)-PHNO