title: PET imaging reveals sex differences in kappa opioid receptor availability in humans, in vivo.
abstract: Opioid receptors may play critical roles in alcoholism and other addictions, addiction withdrawal, and depression and are considered pharmacological targets for treatment of these conditions. Sex differences have been demonstrated in mu (MOR) and delta (DOR) opioid receptors in humans, in vivo. In addition, sex differences have been observed in efficacy of treatment targeting kappa opioid receptors (KOR). Our goal in the present study was to compare the availability of KOR (1) between healthy control (HC) men and women. Twenty-seven subjects-18 males (M) and 9 females (F)-underwent PET scans with [(11)C] LY2795050, a selective kappa antagonist tracer. Partial volume correction was applied to all PET data. Volume of distribution (V T) of the tracer was estimated regionally as well as at the voxel level. V T values of males versus females were compared for 19 defined ROIs. Results at the regional and voxel levels were consistent. Males had significantly higher V T and thus a higher KOR availability than women in multiple brain regions. To our knowledge, this is the first report of sex differences in the KOR system in humans, in vivo. These findings could have implications for the treatment of pain with kappa opioid analgesics. The results may also have an impact on the diagnosis and treatment of addictive and other disorders.
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale Universit New Haven, CT, USA.
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Vijay
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale UniversitNew Haven, CT, USA; Department of Biomedical Engineering, Yale UniversityNew Haven, CT, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale Universit New Haven, CT, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Worhunsky
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale Universit New Haven, CT, USA.
authors.forename: Ming-Qiang
authors.initials: MQ
authors.lastname: Zheng
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale Universit New Haven, CT, USA.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Nabulsi
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale Universit New Haven, CT, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Ropchan
authors.affiliation: Department of Biomedical Engineering, Yale University New Haven, CT, USA.
authors.forename: Suchitra
authors.initials: S
authors.lastname: Krishnan-Sarin
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale Universit New Haven, CT, USA.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale UniversitNew Haven, CT, USA; Department of Biomedical Engineering, Yale UniversityNew Haven, CT, USA; Department of Psychiatry, Yale UniversityNew Haven, CT, USA.
authors.forename: Evan D
authors.initials: ED
authors.lastname: Morris
keywords: PET imaging; Sex differences; kappa opioid receptor system; volume of distribution