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 ¼ 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 ¼ 0.02) and putamen (11.6% difference, p ¼ 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.

Hippocampal volume and functional connectivity changes during the female menstrual cycle

“…The variations of female sex hormones over the menstrual cycle in mammals are connected to neural changes, including structural as well as functional transformations in different brain regions (e.g., Czoty et al, 2009;Desmond and Levy, 1997;Olmos et al, 1989;Qiu et al, 2013;Woolley, 1998;Woolley and McEwen, 1993). Estrogen and progesterone, the two main ovarian steroids, have received most attention in this research field.…”

La Escala Multidimensional de Craving de Alcohol y el SPECT con yodobenzamida[I123] como predictores de recaída precoz en pacientes que presentan dependencia del alcohol

“…Con la finalidad de obtener una muestra homogénea de personas con dependencia del alcohol se incluyeron pacientes que reunían los siguientes criterios: (A) un elevado craving de alcohol basal superior a 40 puntos de la escala EMCA, que corresponde al cuartil superior y estaría asociado a una elevada vulnerabilidad hacia la recaída precoz; (B) hombres, por tener una mayor estabilidad que las mujeres, con respecto a la disponibilidad de receptores dopaminérgicos D2 en el estriado 16 ; y (C) de edades comprendidas entre los 40 y los 55 años, dado que la disponibilidad de receptores D2 experimenta un progresivo declive con la edad 17,18 . Los criterios de exclusión han sido la presencia de un grave trastorno médico, psiquiátrico o neurológico, deterioro cognitivo, hipersensibilidad a fármacos como el yolopride, el yodo o el perclorato potásico; haber sido tratado con agonistas o antagonistas dopaminérgicos durante los 3 meses previos y reunir los criterios DSM-IV-TR para el abuso o dependencia de otras sustancias que no fueran el alcohol, la nicotina o la cafeína, durante los últimos 6 meses.…”

“…To obtain a homogeneous sample of alcohol-dependent persons we included patients who met the following criteria: (A) alcohol craving in MACS scale above 40 points; this is the highest score quartile and vulnerability to early relapse is possibly high; (B) males: D2 receptor availability in the striatum is more stable in males than in females 16 ; and (C) age 40 to 55 years, as D2 receptor availability declines with age 17,18 .…”

Variability in paralimbic dopamine signaling correlates with subjective responses to D-amphetamine

“…Furthermore, all females were tested in the early follicular phase of their menstrual cycle on both PET scan days and no hormone that we measured (plasma estrogen, estradiol, or progesterone) significantly differed between female Responders or Nonresponders on either PET scan day. Given literature suggesting a potential relationship between female hormones and DA signaling (Bazzett and Becker, 1994;Becker, 1990;Czoty et al, 2009;Di Paolo et al, 1988;McDermott et al, 1994;Nordstrom et al, 1998), though, the role of female hormone effects on PET measures of DA signaling should be investigated in future studies.…”