Using Quantitative Hormone Monitoring to Identify the Postpartum Return of Fertility.

Background and Objectives: The Marquette Method (MM) has been used for many years to track the postpartum return of fertility using the ClearBlue Fertility Monitor (CBFM). A new quantitative urine hormone monitor (the Mira Analyzer) was compared to the CBFM in one previous study, and using this pilot data, several women have started to use the Mira Analyzer in the postpartum transition to fertility. Materials and Methods: This study was a retrospective, observational case series that analyzed hormone data on the Mira Analyzer during the postpartum period. Participants were invited to share their postpartum cycle and hormone observations. Quantitative hormones in the urine included estrone-3-glucuronide (E3G), luteinizing hormone (LH), and pregnanediol glucuronide (PDG). Data were collected using an electronic survey and an online portal for hormone data. Data collected included participant demographics, menstrual cycle characteristics, and reproductive health history. Hormone range values were calculated, and thresholds were identified that would best predict the first ovulation that led to the first postpartum menstrual period, as well as in transition cycles. Hormone patterns were identified in the context of previous studies. Results: Twenty participants contributed data for the analysis. Triggering ovulation before the first period postpartum (Cycle 0) usually required higher LH thresholds than for regularly cycling women. Three different patterns were observed in the return of fertility postpartum: minimal ovarian activity, follicular activity without ovulation, and the early return of fertility. Abstinence rates for avoiding pregnancy with experimental thresholds were calculated. Conclusions: Higher LH thresholds in Cycle 0 suggest a decreased responsiveness of the ovaries to LH stimulation from the pituitary. This study replicates postpartum hormone patterns from a previous study. Larger studies are planned to evaluate the effectiveness for avoiding pregnancy using the Mira Analyzer in the postpartum return of fertility.

Case Reports from Women Using a Quantitative Hormone Monitor to Track the Perimenopause Transition.

The fertility tracking of menstrual cycles during perimenopause with a quantitative hormone monitor is a novel undertaking. Women in regular menstrual cycles have been tracking their fertility using different biomarkers since the 1960's. Presently, there are newer electronic hormonal devices used to track fertility that provide more exact and objective data to help delineate the fertile time frame of a woman's cycle. These devices measure quantitative levels of estrogen, the luteinizing hormone, progesterone, and follicle-stimulating hormone, all of which occur at varying levels during the menstrual cycle. As women advance toward menopause, their cycles vary in length, and their hormones fluctuate. In this retrospective analysis, forty-two women aged 40 to 50 tracked their cycles over time, and eight of these forty-two women used the quantitative hormonal device. With the use of this device, the perimenopausal period has revealed distinct hormonal cycle characteristics that are unique to this group of women. It is the purpose of this paper to discuss these cycle's characteristics during perimenopause, which were found with the use of the quantitative hormonal device.

Effectiveness of a Postpartum Breastfeeding Protocol for Avoiding Pregnancy.

The uses of cervical mucus and basal body temperature as indicators of return to fertility postpartum have resulted in high unintended pregnancy rates. In 2013, a study found that when women used urine hormone signs in a postpartum/breastfeeding protocol this resulted in fewer pregnancies. To improve the original protocol's effectiveness, three revisions were made: (1) women were to increase the number of days tested with the Clearblue Fertility Monitor, (2) an optional second luteinizing hormone test could be done in the evening, and (3) instructions were given to manage the beginning of the fertile window for the first six cycles postpartum. The purpose of this study was to determine the correct and typical use effectiveness rates to avoid pregnancy in women who used a revised postpartum/breastfeeding protocol. A cohort review of an established data set from 207 postpartum breastfeeding women who used the protocol to avoid pregnancy was completed using Kaplan-Meier survival analysis. Total pregnancy rates that included correct and incorrect use pregnancies were eighteen per one hundred women over twelve cycles of use. For the pregnancies that met a priori criteria, the correct use pregnancy rates were two per one hundred over twelve months and twelve cycles of use and typical use rates were four per one hundred women at twelve cycles of use. The protocol had fewer unplanned pregnancies than the original, however, the cost of the method increased.

Menstrual Cycle Parameters Are Not Significantly Different After COVID-19 Vaccination.

Background: Some studies have suggested minor changes in the menstrual cycle after COVID-19 vaccination, but more detailed analyses of the menstrual cycle are needed to evaluate more specific changes in the menstrual cycle that are not affected by survey-based recall bias. Materials and Methods: Using a pretest-post-test quasi-experimental evaluation of menstrual cycle parameters before and after COVID-19 vaccination, we conducted an anonymous online survey of two groups of North American women who prospectively monitor their menstrual cycle parameters daily including bleeding patterns, urinary hormone levels using the ClearBlue Fertility Monitor, or cervical mucus observations. The primary outcome measures were cycle length, length of menses, menstrual volume, estimated day of ovulation (EDO), luteal phase length, and signs of ovulation. Perceived (subjective) menstrual cycle changes and stressors were also evaluated in this study as secondary outcome measures. Results: Of the 279 women who initiated the survey, 76 met the inclusion criteria and provided 588 cycles for analysis (227 pre-vaccine cycles, 145 vaccine cycles, 216 post-vaccine cycles). Although 22% of women subjectively identified changes in their menstrual cycle, there were no significant differences in menstrual cycle parameters (cycle length, length of menses, EOD, and luteal phase length) between the pre-vaccine, vaccine, and post-vaccine cycles. Conclusions: COVID-19 vaccines were not associated with significant changes in menstrual cycle parameters. Perceived changes by an individual woman must be compared with statistical changes to avoid confirmation bias.

Examining Web-Based Learning to Enhance Nurse Training and the Standardization of Clinical Practice Within Complex Global Nursing Systems: A Quality Improvement Case Study.

Nurses are the backbone of health assessments and key to safeguarding health services for people who are displaced and migrating. Training and dissemination of information among an international workforce requires innovative delivery methods that address the barriers of traditional in-person training. This quality improvement project endorsed web-based learning as a viable platform to disseminate information and support a standardized approach to professional development of nurses working in a complex and dynamic international healthcare setting.

Neonatal Development in Prenatally Zika Virus-Exposed Infant Macaques with Dengue Immunity.

Infants exposed to Zika virus (ZIKV) prenatally may develop birth defects, developmental deficits, or remain asymptomatic. It is unclear why some infants are more affected than others, although enhancement of maternal ZIKV infection via immunity to an antigenically similar virus, dengue virus (DENV), may play a role. We hypothesized that DENV immunity may worsen prenatal ZIKV infection and developmental deficits in offspring. We utilized a translational macaque model to examine how maternal DENV immunity influences ZIKV-exposed infant macaque neurodevelopment in the first month of life. We inoculated eight macaques with prior DENV infection with ZIKV, five macaques with ZIKV, and four macaques with saline. DENV/ZIKV-exposed infants had significantly worse visual orientation skills than ZIKV-exposed infants whose mothers were DENV-naive, with no differences in motor, sensory or state control development. ZIKV infection characteristics and pregnancy outcomes did not individually differ between dams with and without DENV immunity, but when multiple factors were combined in a multivariate model, maternal DENV immunity combined with ZIKV infection characteristics and pregnancy parameters predicted select developmental outcomes. We demonstrate that maternal DENV immunity exacerbates visual orientation and tracking deficits in ZIKV-exposed infant macaques, suggesting that human studies should evaluate how maternal DENV immunity impacts long-term neurodevelopment.

Quantitative definition of neurobehavior, vision, hearing and brain volumes in macaques congenitally exposed to Zika virus.

Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified the typical pregnancy outcomes of congenital ZIKV infection, with fetal demise and placental abnormalities. We estimated sample sizes needed to define differences between groups and demonstrated that future studies quantifying brain region volumes, retinal structure, hearing, and visual pathway function require a sample size of 14 animals per group (14 ZIKV, 14 control) to detect statistically significant differences in at least half of the infant exam parameters. Establishing the parameters for future studies of neurodevelopmental outcomes following congenital ZIKV exposure in macaques is essential for robust and rigorous experimental design.

PET Measures of D1, D2, and DAT Binding Are Associated With Heightened Tactile Responsivity in Rhesus Macaques: Implications for Sensory Processing Disorder.

Sensory processing disorder (SPD), a developmental regulatory condition characterized by marked under- or over-responsivity to non-noxious sensory stimulation, is a common but poorly understood disorder that can profoundly affect mood, cognition, social behavior and adaptive life skills. Little is known about the etiology and neural underpinnings. Clinical research indicates that children with SPD show greater prevalence of difficulties in complex cognitive behavior including working memory, behavioral flexibility, and regulation of sensory and affective functions, which are related to prefrontal cortex (PFC), striatal, and midbrain regions. Neuroimaging may provide insight into mechanisms underlying SPD, and animal experiments provide important evidence that is not available in human studies. Rhesus monkeys (N = 73) were followed over a 20-year period from birth into old age. We focused on a single sensory modality, the tactile system, measured at 5-7 years, because of its critical importance for nourishment, attachment, and social reward in development. Positron emission tomography imaging was conducted at ages 12-18 years to quantify the availability of the D1 and D2 subtypes of the DA receptor (D1R and D2R), and the DA transporter (DAT). Heightened tactile responsivity was related to (a) elevated D1R in PFC overall, including lateral, ventrolateral, medial, anterior cingulate (aCg), frontopolar, and orbitofrontal (OFC) subregions, as well as nucleus accumbens (Acb), (b) reduced D2R in aCg, OFC, and substantia nigra/ventral tegmental area, and (c) elevated DAT in putamen. These findings suggest a mechanism by which DA pathways may be altered in SPD. These pathways are associated with reward processing and pain regulation, providing top-down regulation of sensory and affective processes. The balance between top-down cognitive control in the PFC-Acb pathway and bottom-up motivational function of the VTA-Acb-PFC pathway is critical for successful adaptive function. An imbalance in these two systems might explain DA-related symptoms in children with SPD, including reduced top-down regulatory function and exaggerated responsivity to stimuli. These results provide more direct evidence that SPD may involve altered DA receptor and transporter function in PFC, striatal, and midbrain regions. More work is needed to extend these results to humans.

Pilot Evaluation of a New Urine Progesterone Test to Confirm Ovulation in Women Using a Fertility Monitor.

Background: Progesterone rises ~24-36 h after ovulation. Past studies using ultrasound-confirmed ovulation have shown that three consecutive tests with a threshold of 5µg/mL of urine progesterone (pregnanediol-3-glucuronide, PDG), taken after the luteinizing hormone (LH) surge, confirmed ovulation with 100% specificity. Purpose: The purpose of this study was to a evaluate a new urine PDG self-test to retrospectively confirm ovulation in women who were monitoring ovulation using a hormonal fertility monitor. Methods: Thirteen women of reproductive age were recruited to test urine PDG while using their home hormonal fertility monitor. The monitor measured the rise in estrogen (estrone-3-glucuronide, E3G) and LH to estimate the fertile phase of the menstrual cycle. The women used an online menstrual cycle charting system to track E3G, LH and PDG levels for four menstrual cycles. Results: The participants (Mean age 33.6) produced 34 menstrual cycles of data (Mean length 28.4 days), 17 of which used a PDG test with a threshold of 7µg/mL and 17 with a threshold of 5µg/mL. In the cycles that used the 7µg/mL test strips, 59% had a positive confirmation of ovulation, and with the 5µg/mL test strips, 82% of them had a positive confirmation of ovulation. Conclusion: The 5µg/mL PDG test confirmed ovulation in 82% of cycles and could assist women in the evaluation of the luteal progesterone rise of their menstrual cycle.

Activation of the sympathetic nervous system suppresses mouse white adipose tissue hyperplasia through the ß1 adrenergic receptor.

Adipose tissue (AT) expands via both hypertrophy and hyperplasia during the development of obesity. While AT hypertrophy involves the increase in size of existing adipocytes, hyperplasia is the process of creating new adipocytes from the pool of adipocyte precursor cells (APCs), which includes adipocyte progenitor cells and preadipocytes. Prior studies have implicated a role of the sympathetic nervous system (SNS) in regulation of hyperplasia in white adipose tissue (WAT). Here, we aimed to determine the mechanisms underlying SNS regulation of APC proliferation in mouse WAT. Using flow cytometry with antibodies against various cell surface markers, along with an intracellular marker of proliferation (Ki67), we quantitated the percentages and proliferative status of adipocyte progenitor cells and preadipocytes in the stromal vascular fraction (SVF) of WAT. In vivo SNS activation through cold exposure, as well as in vitro adrenergic stimulation via exposure to the canonical SNS neurotransmitter norepinephrine (NE), inhibited preadipocyte proliferation. Pretreatment with propranolol, a ß1- and ß2-adrenergic receptor (AR) antagonist, trended toward rescuing the inhibitory effects of NE in primary cell culture. The selective ß1-AR agonist dobutamine diminished preadipocyte proliferation both in vivo and in vitro, whereas the selective ß2-AR agonist, salbutamol, promoted proliferation in vitro, suggesting that the ß1-AR may mediate the inhibitory effect of NE on preadipocyte proliferation. Taken together, we conclude that SNS activation suppresses preadipocyte proliferation via activation of the ß1 AR in WAT.

Cross-species comparison of behavioral neurodevelopmental milestones in the common marmoset monkey and human child.

The common marmoset (Callithrix jacchus) is an increasingly popular non-human primate species for developing transgenic and genomic edited models of neurological disorders. These models present an opportunity to assess from birth the impact of genetic mutations and to identify candidate predictive biomarkers of early disease onset. In order to apply findings from marmosets to humans, a cross-species comparison of typical development is essential. Aiming to identify similarities, differences, and gaps in knowledge of neurodevelopment, we evaluated peer-reviewed literature focused on the first 6 months of life of marmosets and compared to humans. Five major developmental constructs, including reflexes and reactions, motor, feeding, self-help, and social, were compared. Numerous similarities were identified in the developmental sequences with differences often influenced by the purpose of the behavior, specifically for marmoset survival. The lack of detailed knowledge of marmoset development was exposed as related to the vast resources for humans.

Effectiveness of an Online Natural Family Planning Program for Breastfeeding Women.

OBJECTIVE: To analyze the effectiveness of an online, nurse-managed natural family planning (NFP) program among breastfeeding women and subgroups of these women. DESIGN: Longitudinal comparative cohort study. SETTING: A university-based online NFP education program and menstrual cycle charting system. PARTICIPANTS: Women (N = 816) with a mean age of 30.3 years (standard deviation = 4.5) who registered to use the online NFP system and indicated they were breastfeeding. METHODS: Participants tracked their fertile times with an electronic hormone fertility monitor (EHFM), cervical mucus monitoring, or both. All unintended pregnancies were evaluated by professional nurses. RESULTS: The correct use pregnancy rates were 3 per 100 users over 12 cycles of use, and typical rates were 14 per 100 at 12 cycles of use. At 12 cycles of use, total pregnancy rates were 16 per 100 for electronic hormone fertility monitor users (n = 380), 81 per 100 among mucus-only users (n = 45), and 14 per 100 for electronic hormone fertility monitor plus mucus users (n = 391). CONCLUSION: Use of a nurse-managed online NFP program for women can be effective to help women avoid pregnancy while breastfeeding, especially with correct and consistent use.

Effectiveness of a Natural Family Planning Service Program.

PURPOSE: The aims of this study were to determine and compare extended use-effectiveness of an online nurse-managed fertility education service program among women (and subgroups of women) seeking to avoid pregnancy. STUDY DESIGN AND METHODS: This was a 24-month prospective study of a university-based online Web site with 663 nonbreastfeeding women using an online charting system to avoid pregnancy. Participants tracked their fertility online with either cervical mucus monitoring, electronic hormonal fertility monitoring, or both fertility indicators. Unintended pregnancies were validated by professional nurses. RESULTS: Participants had a mean age of 30.4 years (SD = 6.3) and mean 1.7 children (SD = 2.0). Among the 663 nonbreastfeeding participants there were 2 unintended pregnancies per 100 at 24 cycles of correct use and 15 pregnancies at 24 cycles of typical use. However, the 212 women using the electronic fertility monitor had a typical use unintended pregnancy rate of 6 at 24 cycles of use in comparison with the 118 women using cervical mucus monitoring that had a typical use pregnancy rate of 19 at 24 cycles and with the 333 women using both fertility indicators that had a pregnancy rate of 18 at 24 cycles of use. CLINICAL IMPLICATIONS: Use of the fertility monitor to estimate fertility among nonbreastfeeding women provides the most secure method of avoiding pregnancy.

Achieving Pregnancy Using Primary Care Interventions to Identify the Fertile Window.

OBJECTIVE: To determine the effectiveness of achieving pregnancy with focused intercourse in the fertile window identified using natural fertility indicators. METHODS: 24-cycle prospective effectiveness study. SETTING: A North American web-based fertility monitoring service. PARTICIPANTS: 256 North American women aged 20-43 (mean age 29.2 years) seeking to achieve pregnancy. INTERVENTION: Participants identified their fertile window with either electronic hormonal fertility monitoring or cervical mucus monitoring, or both, and recorded their observations on an online fertility tracking system. MAIN OUTCOME MEASURES: Pregnancies were validated by nurses with an online self-assessed pregnancy evaluation form. Survival analysis was used to determine pregnancy rates. RESULTS: There were 150 pregnancies among the 256 participants with an overall pregnancy rate of 78 per 100 women over 12 menstrual cycles. There were 54 pregnancies (68%) among the 80 women using the fertility monitor, 11 pregnancies (46%) among the 24 women using mucus monitoring, and 90 (63%) among the 143 women using both mucus and monitor. The 12-cycle pregnancy rates per 100 women were 83 (monitor group), 72 (mucus group), and 75 (mucus and monitor group). Pregnancy rates reached 100% at 24 cycles of use for those women using the hormonal fertility monitor. CONCLUSION: Use of the hormonal fertility monitor alone seems to offer the best natural estimate of the fertile phase of the menstrual cycle for women wishing to achieve a pregnancy. Focusing intercourse through 24 menstrual cycles can be beneficial for achieving pregnancy.

Sensory Processing in Rhesus Monkeys: Developmental Continuity, Prenatal Treatment, and Genetic Influences.

Neonatal sensory processing (tactile and vestibular function) was tested in 78 rhesus macaques from two experiments. At ages 4-5 years, striatal dopamine D2 receptor binding was examined using positron emission tomography. At ages 5-7 years, adult sensory processing was assessed. Findings were: (a) prenatal stress exposure yielded less optimal neonatal sensory processing; (b) animals carrying the short rh5-HTTLPR allele had less optimal neonatal sensory scores than monkeys homozygous for the long allele; (c) neonatal sensory processing was significantly related to striatal D2 receptor binding for carriers of the short allele, but not for animals homozygous for the long allele; and (d) there was moderate developmental continuity in sensory processing from the neonatal period to adulthood.

The Effects of a Single Developmentally Entrained Pulse of Testosterone in Female Neonatal Mice on Reproductive and Metabolic Functions in Adult Life.

Early postnatal exposures to sex steroids have been well recognized to modulate predisposition to diseases of adulthood. There is a complex interplay between timing, duration and dose of endocrine exposures through environmental or dietary sources that may alter the sensitivity of target tissues to the exogenous stimuli. In this study, we determined the metabolic and reproductive programming effects of a single developmentally entrained pulse of testosterone (T) given to female mice in early postnatal period. CD-1 female mice pups were injected with either 5 µg of T enanthate (TE) or vehicle (control [CON] group) within 24 hours after birth and followed to adult age. A total of 66% of T-treated mice exhibited irregular cycling, anovulatory phenotype, and significantly higher ovarian weights than vehicle-treated mice. Longitudinal nuclear magnetic resonance measurements revealed that TE group had greater body weight, whole-body lean, and fat mass than the CON group. Adipose tissue cellularity analysis in TE group revealed a trend toward higher size and number than their littermate CONs. The brown adipose tissue of TE mice exhibited white fat infiltration with down-regulation of several markers, including uncoupling protein 1 (UCP-1), cell death-inducing DNA fragmentation factor, α-subunit-like effector A, bone morphogenetic protein 7 as well as brown adipose tissue differentiation-related transcription regulators. T-injected mice were also more insulin resistant than CON mice. These reproductive and metabolic reprogramming effects were not observed in animals exposed to TE at 3 and 6 weeks of age. Collectively, these data suggest that sustained reproductive and metabolic alterations may result in female mice from a transient exposure to T during a narrow postnatal developmental window.

Development of a novel postnatal neurobehavioral scale for evaluation of common marmoset monkeys.

Common marmoset (Callithrix jacchus) monkeys when compared to rhesus macaques (Macaca mullatta) present several advantages for disease modeling, especially transgenic initiatives, as they commonly give birth to twins, which increases sample size, have accelerated development and a shorter life span that facilitates the analysis of the onset of age-related diseases. Yet, no tools are currently available to assess marmoset neurodevelopment during the initial first month of life. Here we report the creation of a novel Primate Postnatal Neurobehavioral Assessment Scale for marmoset monkeys (PPNAS-M) that was based on currently available scales for human and rhesus monkeys. Twenty-four healthy marmoset infants (12 females, 12 males) from 12 families were evaluated. The infant assessments involved 10-minute testing administered at 15 and 30 days after birth. The PPNAS-M consists of 41 noninvasive tests grouped into 5 testing categories: visual orienting, auditory and spatial orienting, motor responses, righting and body strength, and temperament tests. Testing at these two ages did not affect the overall health of the infants, suggesting that the PPNAS-M is a non-invasive testing tool. Significant maturation was demonstrated by increased scores in each of the five testing categories from postnatal day 15 to 30, with developmental patterns unique to marmosets. Principal component analysis defined 4 item groups (Orientation, State Control, Motor Maturity and Sensory Sensitivity) with 5 variables each. Orientation and State Control factors were highly similar to each other at both ages and correlated highly with previous item groupings used with rhesus macaques. Our results indicate that the PPNAS-M is a useful assessment tool for detecting neuromotor, attention, and temperament status of infant marmosets and that it is sensitive to developmental effects. Further studies to validate the PPNAS-M for the assessment of normal development versus early effects of developmental perturbations associated to prenatal exposures and transgenesis are warranted.

The effects of chronic alcohol self-administration on serotonin-1A receptor binding in nonhuman primates.

BACKGROUND: Previous studies have found interrelationships between the serotonin system and alcohol self-administration. The goal of this work was to directly observe in vivo effects of chronic ethanol self-administration on serotonin 5-HT1A receptor binding with [(18)F]mefway PET neuroimaging in rhesus monkeys. Subjects were first imaged alcohol-naïve and again during chronic ethanol self-administration to quantify changes in 5-HT1A receptor binding. METHODS: Fourteen rhesus monkey subjects (10.7-12.8 years) underwent baseline [(18)F]mefway PET scans prior to alcohol exposure. Subjects then drank gradually increasing ethanol doses over four months as an induction period, immediately followed by at least nine months ad libidum ethanol access. A post [(18)F]mefway PET scan was acquired during the final three months of ad libidum ethanol self-administration. 5-HT1A receptor binding was assayed with binding potential (BPND) using the cerebellum as a reference region. Changes in 5-HT1A binding during chronic ethanol self-administration were examined. Relationships of binding metrics with daily ethanol self-administration were also assessed. RESULTS: Widespread increases in 5-HT1A binding were observed during chronic ethanol self-administration, independent of the amount of ethanol consumed. A positive correlation between 5-HT1A binding in the raphe nuclei and average daily ethanol self-administration was also observed, indicating that baseline 5-HT1A binding in this region predicted drinking levels. CONCLUSIONS: The increase in 5-HT1A binding levels during chronic ethanol self-administration demonstrates an important modulation of the serotonin system due to chronic alcohol exposure. Furthermore, the correlation between 5-HT1A binding in the raphe nuclei and daily ethanol self-administration indicates a relationship between the serotonin system and alcohol self-administration.

Initial in vivo PET imaging of 5-HT1A receptors with 3-[(18)F]mefway.

4-trans-[(18)F]Mefway is a PET radiotracer with high affinity for 5-HT1A receptors. Our preliminary work indicated the positional isomer, 3-[(18)F]mefway, would be suitable for PET imaging of 5-HT1A receptors. We now compare the in vivo behaviour of 3-mefway with 4-mefway to evaluate 3-[(18)F]mefway as a potential 5-HT1A PET radiotracer. Two male rhesus macaques were given bolus injections of both 3- and 4-trans-[(18)F]mefway in separate experiments. 90 minute dynamic PET scans were acquired. TACs were extracted in the mesial temporal lobe (MTL) and caudal anterior cingulate gyrus (cACg). The cerebellum (CB) was used as a reference region. In vivo behavior of the radiotracers in the CB was compared based upon the ratio of normalized PET uptake for 3- and 4-trans-[(18)F]mefway. Specific binding was compared by examining MTL/CB and cACg/CB ratios. The subject-averaged ratio of 3-[(18)F]mefway to 4-trans-[(18)F]mefway in the cerebellum was 0.96 for 60-90 minutes. MTL/CB reached plateaus of ~2.7 and ~6 by 40 minutes and 90 minutes for 3- and 4-trans-[(18)F]mefway, respectively. cACg/CB reached plateaus of ~2.5 and ~6 by 40 minutes and 70 minutes for 3- and 4-trans-[(18)F]mefway, respectively. The short pseudoequilibration times and sufficient uptake of 3-[(18)F]mefway may be useful in studies requiring short scan times. Furthermore, the similar nondisplaceable clearance in the CB to 4-trans-[(18)F]mefway suggests the lower BPND of 3-[(18)F]mefway is due to a lower affinity. The lower affinity of 3-[(18)F]mefway may make it useful for measuring changes in endogenous 5-HT levels, however, this remains to be ascertained.

Changes in the α4ß2* nicotinic acetylcholine system during chronic controlled alcohol exposure in nonhuman primates.

BACKGROUND: The precise nature of modifications to the nicotinic acetylcholine receptor (nAChR) system in response to chronic ethanol exposure is poorly understood. The present work used PET imaging to assay α4ß2* nAChR binding levels of eight rhesus monkeys before and during controlled chronic ethanol intake. METHODS: [(18)F]Nifene PET scans were conducted prior to alcohol exposure, and then again after at least 8 months controlled ethanol exposure, including 6 months at 1.5 g/kg/day following a dose escalation period. Receptor binding levels were quantified with binding potentials (BPND) using the cerebellum as a reference region. Alcohol self-administration was assessed as average daily alcohol intake during a 2 month free drinking period immediately following controlled alcohol. RESULTS: Significant decreases in α4ß2* nAChR binding were observed in both frontal and insular cortex in response to chronic ethanol exposure. During chronic alcohol exposure, BPND in the lateral geniculate region correlated positively with the amount of alcohol consumed during free drinking. CONCLUSIONS: The observed decreases in nAChR availability following chronic alcohol consumption suggest alterations to this receptor system in response to repeated alcohol administration, making this an important target for further study in alcohol abuse and alcohol and nicotine codependence.