title: Effect of menstrual cycle phase on dopamine D2 receptor availability in female cynomolgus monkeys.
abstract: Sex differences have been reported in a variety of affective and neurodegenerative disorders that involve dysfunctional dopamine (DA) neurotransmission. In addition, there is evidence for differences in sensitivity to the abuse-related effects of psychostimulants across the menstrual cycle which may result from effects of ovarian hormones on DA function. The goal of the present study was to extend previous work examining menstrual cycle-related changes in DA D2 receptor availability in humans to drug-naive female cynomolgus monkeys (n=7) using the selective D2-like receptor ligand [(18)F]fluoroclebopride (FCP) and a high-resolution microPET P4 scanner. Menstrual cycle phase was characterized by daily vaginal swabs and measurements of serum progesterone levels. PET studies were conducted once during the luteal phase and once during the follicular phase. Regions of interest in the caudate nucleus, putamen, and cerebellum were defined on coregistered MRIs. Distribution volumes were calculated for FCP in each structure and the distribution volume ratio (DVR) for both brain regions relative to the cerebellum was used as a measure of D2 receptor availability. FCP DVRs were significantly higher in the luteal phase compared to the follicular phase in both the caudate nucleus (11.7% difference, p=0.02) and putamen (11.6% difference, p=0.03). These findings extend earlier work in humans and suggest that changes in DA receptor availability may be involved in the variation in symptoms of various neuropsychiatric disorders across the menstrual cycle, including differences in sensitivity to the abuse-related effects of stimulants.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Czoty
authors.forename: Natallia V
authors.initials: NV
authors.lastname: Riddick
authors.forename: H Donald
authors.initials: HD
authors.lastname: Gage
authors.forename: Mikki
authors.initials: M
authors.lastname: Sandridge
authors.forename: Susan H
authors.initials: SH
authors.lastname: Nader
authors.forename: Sudha
authors.initials: S
authors.lastname: Garg
authors.forename: Michael
authors.initials: M
authors.lastname: Bounds
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Garg
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nader
mesh_terms: D000818:Animals; D001549:Benzamides; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D005498:Follicular Phase / Q000502:physiology; D008183:Luteal Phase / Q000502:physiology; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D008597:Menstrual Cycle / Q000378:metabolism* / Q000502:physiology; D010880:Piperidines; D049268:Positron-Emission Tomography; D011374:Progesterone / Q000097:blood; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*
chemical_list: D001549:Benzamides; D010880:Piperidines; D017448:Receptors, Dopamine D2; C083673:fluoroclebopride; D011374:Progesterone