Generative artificial intelligence chatbots may provide appropriate informational responses to common vascular surgery questions by patients.

OBJECTIVES: Generative artificial intelligence (AI) has emerged as a promising tool to engage with patients. The objective of this study was to assess the quality of AI responses to common patient questions regarding vascular surgery disease processes. METHODS: OpenAI's ChatGPT-3.5 and Google Bard were queried with 24 mock patient questions spanning seven vascular surgery disease domains. Six experienced vascular surgery faculty at a tertiary academic center independently graded AI responses on their accuracy (rated 1-4 from completely inaccurate to completely accurate), completeness (rated 1-4 from totally incomplete to totally complete), and appropriateness (binary). Responses were also evaluated with three readability scales. RESULTS: ChatGPT responses were rated, on average, more accurate than Bard responses (3.08 ± 0.33 vs 2.82 ± 0.40, p < .01). ChatGPT responses were scored, on average, more complete than Bard responses (2.98 ± 0.34 vs 2.62 ± 0.36, p < .01). Most ChatGPT responses (75.0%, n = 18) and almost half of Bard responses (45.8%, n = 11) were unanimously deemed appropriate. Almost one-third of Bard responses (29.2%, n = 7) were deemed inappropriate by at least two reviewers (29.2%), and two Bard responses (8.4%) were considered inappropriate by the majority. The mean Flesch Reading Ease, Flesch-Kincaid Grade Level, and Gunning Fog Index of ChatGPT responses were 29.4 ± 10.8, 14.5 ± 2.2, and 17.7 ± 3.1, respectively, indicating that responses were readable with a post-secondary education. Bard's mean readability scores were 58.9 ± 10.5, 8.2 ± 1.7, and 11.0 ± 2.0, respectively, indicating that responses were readable with a high-school education (p < .0001 for three metrics). ChatGPT's mean response length (332 ± 79 words) was higher than Bard's mean response length (183 ± 53 words, p < .001). There was no difference in the accuracy, completeness, readability, or response length of ChatGPT or Bard between disease domains (p > .05 for all analyses). CONCLUSIONS: AI offers a novel means of educating patients that avoids the inundation of information from "Dr Google" and the time barriers of physician-patient encounters. ChatGPT provides largely valid, though imperfect, responses to myriad patient questions at the expense of readability. While Bard responses are more readable and concise, their quality is poorer. Further research is warranted to better understand failure points for large language models in vascular surgery patient education.

Environmental Exposure Assessment: Considerations for Oncology Nurses.

Certain patients with cancer are eligible for exposure-related cancer compensation through federal programs, class action lawsuits, or employer programs. However, clinical tools for oncology nurses often do not include prompt.

The Effects of a Caregiver Implemented Toilet Training Package.

Toileting skills are a milestone typically achieved by the age of four. For many caregivers, particularly those who have children diagnosed with autism spectrum disorder or other developmental disabilities, teaching toileting is a challenge resulting in delayed implementation. Delaying toileting increases the risk of challenges to acquiring this skill. Caregivers are fundamental and research shows that their involvement supports the maintenance and sustainability of this skill. Four caregivers were taught a 24-step toilet training program to teach toileting. Behaviors measured included urination success, urine accident frequency, and child requests for the bathroom. All caregivers learned the 24-step procedure and the toilet training package was effective in teaching three of the four children daytime urine continence.

Costs and Implementation Effectiveness of Generalist Versus Specialist Models for Adolescent Screening and Brief Intervention in Primary Care.

OBJECTIVE: This study analyzed the marginal service and program costs, and conducted a cost-effectiveness analysis (CEA) of two models of implementation of adolescent substance screening, brief intervention, and referral to treatment (SBIRT). METHOD: SBIRT was implemented at seven clinics in a multisite, cluster-randomized trial, through a Specialist model (behavioral health counselor-delivered brief intervention), and a Generalist model (primary care provider-delivered brief intervention). The CEA calculated marginal costs using an activity-based costing methodology for direct SBIRT services, and effectiveness was measured by the proportion of brief interventions delivered among patients who screened positive for alcohol, tobacco, or other drugs. Site-level program costs comprised start-up and maintenance (training and technical assistance). Costs were estimated in 2017 U.S. dollars. RESULTS: The marginal cost of SBIRT per patient with a positive screen for brief intervention was $6.72 in the Specialist model and $6.05 in the Generalist model. Implementation effectiveness was 7.2% (SE = 2.9%) in the Specialist model and 37.7% (SE = 5.6%) in the Generalist model. The program costs to provide SBIRT for 1 year per site were $13,548 for the Specialist site and $12,081 for the Generalist. CONCLUSIONS: The Generalist model was more effective in implementing brief intervention and less expensive than the Specialist model. Results were robust to sensitivity analysis. Brief intervention delivered by primary care providers rather than by handoff to a behavioral health counselor may ensure greater penetration and a lower cost of these services in primary care settings.

Time course of 3D fibrocartilage formation by expanded human meniscus fibrochondrocytes in hypoxia.

Adult human meniscus fibrocartilage is avascular and nonhealing after injury. Meniscus tissue engineering aims to replace injured meniscus with lab-grown fibrocartilage. Dynamic culture systems may be necessary to generate fibrocartilage of sufficient mechanical properties for implantation; however, the optimal static preculture conditions before initiation of dynamic culture are unknown. This study thus investigated the time course of fibrocartilage formation by human meniscus fibrochondrocytes on a three-dimensional biomaterial scaffold under various static conditions. Human meniscus fibrochondrocytes from partial meniscectomy were expanded to passage 1 (P1) or P2 (3.0 ± 0.4 and 6.5 ± 0.6 population doublings), seeded onto type I collagen scaffolds, and grown in hypoxia (HYP, 3% O2 ) or normoxia (NRX, 20% O2 ) for 3, 6, and 9 weeks. Mechanical properties were not different between P1 and P2 cell-based constructs. Mechanical properties were lower in HYP, increased continually in NRX only, and were positively correlated with glycosaminoglycan content and accumulation of hyaline cartilage-like matrix components. The most mechanically competent tissues (NRX/9 weeks) reached 1/5 of the native meniscus instantaneous compression modulus but had an increasingly hypertrophic matrix-forming phenotype. HYP consistently suppressed the hypertrophic phenotype. The results provide baselines of engineered meniscus fibrocartilage properties under static conditions, which can be used to select a preculture strategy for dynamic culture depending on the desired combination of mechanical properties, hyaline cartilage-like matrix abundance, and hypertrophic phenotype.

Patient Assessment: Using the Oncology Nurse Navigator Patient Assessment for Rural and Other Resource-Poor Settings.

Oncology nurse navigators (ONNs) rely on assessment tools to identify patient priorities so that care may be expedited along the cancer continuum. Few nonproprietary assessment tools exist for ONNs who work in rural and other resource-poor settings to reliably identify and track patient needs and barriers for seamless and timely oncology care.

Myelin Basic Protein and Cardiac Sympathetic Neurodegeneration in Nonhuman Primates.

Minimal myelination is proposed to be a contributing factor to the preferential nigral neuronal loss in Parkinson's disease (PD). Similar to nigral dopaminergic neurons, sympathetic neurons innervating the heart have long, thin axons which are unmyelinated or minimally myelinated. Interestingly, cardiac sympathetic loss in PD is heterogeneous across the heart, yet the spatial relationship between myelination and neurodegeneration is unknown. Here, we report the mapping of myelin basic protein (MBP) expression across the left ventricle of normal rhesus macaques (n = 5) and animals intoxicated with systemic 6-OHDA (50 mg/kg iv) to model parkinsonian cardiac neurodegeneration (n = 10). A subset of 6-OHDA-treated rhesus received daily dosing of pioglitazone (5 mg/kg po; n = 5), a PPARγ agonist with neuroprotective properties. In normal animals, MBP-immunoreactivity (-ir) was identified surrounding approximately 14% of axonal fibers within nerve bundles of the left ventricle, with more myelinated nerve fibers at the base level of the left ventricle than the apex (p < 0.014). Greater MBP-ir at the base was related to a greater number of nerve bundles at that level relative to the apex (p < 0.05), as the percent of myelinated nerve fibers in bundles was not significantly different between levels of the heart. Cardiac sympathetic loss following 6-OHDA was associated with decreased MBP-ir in cardiac nerve bundles, with the percent decrease of MBP-ir greater in the apex (84.5%) than the base (52.0%). Interestingly, cardiac regions and levels with more MBP-ir in normal animals showed attenuated sympathetic loss relative to areas with less MBP-ir in 6-OHDA + placebo (r = -0.7, p < 0.014), but not in 6-OHDA + pioglitazone (r = -0.1) subjects. Our results demonstrate that myelination is present around a minority of left ventricle nerve bundle fibers, is heterogeneously distributed in the heart of rhesus macaques, and has a complex relationship with cardiac sympathetic neurodegeneration and neuroprotection.

Correction: Engineered human meniscus' matrix-forming phenotype is unaffected by low strain dynamic compression under hypoxic conditions.

[This corrects the article DOI: 10.1371/journal.pone.0248292.].

Engineered human meniscus' matrix-forming phenotype is unaffected by low strain dynamic compression under hypoxic conditions.

Low oxygen and mechanical loading may play roles in regulating the fibrocartilaginous phenotype of the human inner meniscus, but their combination in engineered tissues remains unstudied. Here, we investigated how continuous low oxygen ("hypoxia") combined with dynamic compression would affect the fibrocartilaginous "inner meniscus-like" matrix-forming phenotype of human meniscus fibrochondrocytes (MFCs) in a porous type I collagen scaffold. Freshly-seeded MFC scaffolds were cultured for 4 weeks in either 3 or 20% O2 or pre-cultured for 2 weeks in 3% O2 and then dynamically compressed for 2 weeks (10% strain, 1 Hz, 1 h/day, 5 days/week), all with or without TGF-ß3 supplementation. TGF-ß3 supplementation was found necessary to induce matrix formation by MFCs in the collagen scaffold regardless of oxygen tension and application of the dynamic compression loading regime. Neither hypoxia under static culture nor hypoxia combined with dynamic compression had significant effects on expression of specific protein and mRNA markers for the fibrocartilaginous matrix-forming phenotype. Mechanical properties significantly increased over the two-week loading period but were not different between static and dynamic-loaded tissues after the loading period. These findings indicate that 3% O2 applied immediately after scaffold seeding and dynamic compression to 10% strain do not affect the fibrocartilaginous matrix-forming phenotype of human MFCs in this type I collagen scaffold. It is possible that a delayed hypoxia treatment and an optimized pre-culture period and loading regime combination would have led to different outcomes.

Post mortem evaluation of inflammation, oxidative stress, and PPARγ activation in a nonhuman primate model of cardiac sympathetic neurodegeneration.

Cardiac dysautonomia is a common nonmotor symptom of Parkinson's disease (PD) associated with loss of sympathetic innervation to the heart and decreased plasma catecholamines. Disease-modifying strategies for PD cardiac neurodegeneration are not available, and biomarkers of target engagement are lacking. Systemic administration of the catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) recapitulates PD cardiac dysautonomia pathology. We recently used positron emission tomography (PET) to visualize and quantify cardiac sympathetic innervation, oxidative stress, and inflammation in adult male rhesus macaques (Macaca mulatta; n = 10) challenged with 6-OHDA (50mg/kg; i.v.). Twenty-four hours post-intoxication, the animals were blindly and randomly assigned to receive daily doses of the peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone (n = 5; 5mg/kg p.o.) or placebo (n = 5). Quantification of PET radioligand uptake showed increased oxidative stress and inflammation one week after 6-OHDA which resolved to baseline levels by twelve weeks, at which time pioglitazone-treated animals showed regionally preserved sympathetic innervation. Here we report post mortem characterization of heart and adrenal tissue in these animals compared to age and sex matched normal controls (n = 5). In the heart, 6-OHDA-treated animals showed a significant loss of sympathetic nerve fibers density (tyrosine hydroxylase (TH)-positive fibers). The anatomical distribution of markers of sympathetic innervation (TH) and inflammation (HLA-DR) significantly correlated with respective in vivo PET findings across left ventricle levels and regions. No changes were found in alpha-synuclein immunoreactivity. Additionally, CD36 protein expression was increased at the cardiomyocyte intercalated discs following PPARγ-activation compared to placebo and control groups. Systemic 6-OHDA decreased adrenal medulla expression of catecholamine producing enzymes (TH and aromatic L-amino acid decarboxylase) and circulating levels of norepinephrine, which were attenuated by PPARγ-activation. Overall, these results validate in vivo PET findings of cardiac sympathetic innervation, oxidative stress, and inflammation and illustrate cardiomyocyte CD36 upregulation as a marker of PPARγ target engagement.

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.

Hypoxia and TGF-ß3 Synergistically Mediate Inner Meniscus-Like Matrix Formation by Fibrochondrocytes.

IMPACT STATEMENT: The interactions of hypoxia and TGF-ß3 in aggregates of human meniscus fibrochondrocytes are synergistic in nature, suggesting combinatorial strategies using these factors are promising for tissue engineering the inner meniscus regions. Hypoxia alone in the absence of TGF-ß supplementation may be insufficient to initiate an inner meniscus-like extracellular matrix-forming response in this model.

In vivo imaging of inflammation and oxidative stress in a nonhuman primate model of cardiac sympathetic neurodegeneration.

Loss of cardiac postganglionic sympathetic innervation is a characteristic pathology of Parkinson's disease (PD). It progresses over time independently of motor symptoms and is not responsive to typical anti-parkinsonian therapies. Cardiac sympathetic neurodegeneration can be mimicked in animals using systemic dosing of the neurotoxin 6-hydroxydopamine (6-OHDA). As in PD, 6-OHDA-induced neuronal loss is associated with increased inflammation and oxidative stress. To assess the feasibility of detecting changes over time in cardiac catecholaminergic innervation, inflammation, and oxidative stress, myocardial positron emission tomography with the radioligands [11C]meta-hydroxyephedrine (MHED), [11C]PBR28 (PBR28), and [61Cu]diacetyl-bis(N(4))-methylthiosemicarbazone (ATSM) was performed in 6-OHDA-intoxicated adult, male rhesus macaques (n = 10; 50 mg/kg i.v.). The peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone, which is known to have anti-inflammatory and anti-oxidative stress properties, was administered to five animals (5 mg/kg, PO); the other five were placebo-treated. One week after 6-OHDA, cardiac MHED uptake was significantly reduced in both groups (placebo, 86% decrease; pioglitazone, 82%); PBR28 and ATSM uptake increased in both groups but were attenuated in pioglitazone-treated animals (PBR28 Treatment × Level ANOVA p < 0.002; ATSM Mann-Whitney p = 0.032). At 12 weeks, partial recovery of MHED uptake was significantly greater in the pioglitazone-treated group, dependent on left ventricle circumferential region and axial level (Treatment × Region × Level ANOVA p = 0.034); 12-week MHED uptake significantly correlated with tyrosine hydroxylase immunoreactivity across cardiac anatomy (p < 0.000002). PBR28 and ATSM uptake returned to baseline levels by 12 weeks. These radioligands thus hold potential as in vivo biomarkers of mechanisms of cardiac neurodegeneration and neuroprotection.

Convergent and criterion validity of the CogState computerized brief battery cognitive assessment in women with and without breast cancer.

OBJECTIVE: Computerized tests have increasingly garnered interest for assessing cognitive functioning due to their potential logistical and financial advantages over traditional 'pencil and-paper' neuropsychological tests. However, psychometric information is necessary to guide decisions about their clinical and research utility with varied populations. We explored the convergent construct validity and criterion validity of the CogState computerized tests in breast cancer survivors, a group known to present with mostly mild, subtle cognitive dysfunction. METHOD: Fifty-three post-menopausal women (26 breast cancer survivors, 27 healthy controls) completed the CogState Brief Battery tests with passed performance checks, conceptually matched traditional neuropsychological tests, and a self-report measure of daily functioning, the Functional Activities Questionnaire. RESULTS: Significant positive correlations were found between the CogState Brief Battery tests and traditional neuropsychological tests, although the traditional tests specifically hypothesized to correlate with CogState tests did not reach statistical significance. Analysis of Covariance results showed preliminary support for criterion validity, as the patient and control groups differed on the traditional test of working memory (Digits Backwards, p = .01), with a trend towards significance for the CogState test of working memory (One Back, p = .02), controlled for age, race, and mood. CONCLUSIONS: The results provide preliminary support for further research to determine if the CogState tests are viable as screening tools to detect subtle cognitive differences between breast cancer survivors and healthy women. Our study was limited by the low base rate of cognitive impairment and small sample size. We recommend further research employing sufficiently powered sample sizes and a longitudinal, repeated measures study design.

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.

Principal components analysis to identify influences on research communication and engagement during an environmental disaster.

OBJECTIVES: To discern community attitudes towards research engagement in Libby, Montana, the only Superfund site for which a public health emergency has been declared. STUDY DESIGN: Survey study of convenience samples of residents near the Libby, Montana Superfund site. PARTICIPANTS: Residents of the Libby, Montana area were recruited from a local retail establishment (N=120, survey 1) or a community event (N=127, survey 2). MEASURES: Two surveys were developed in consultation with a Community Advisory Panel. RESULTS: Principal components of survey 1 showed four dimensions of community members' attitudes towards research engagement: (1) researcher communication and contributions to the community, (2) identity and affiliation of the researchers requesting participation, (3) potential personal barriers, including data confidentiality, painful or invasive procedures and effects on health insurance and (4) research benefits for the community, oneself or family. The score on the first factor was positively related to desire to participate in research (r=0.31, p=0.01). Scores on factors 2 and 3 were higher for those with diagnosis of asbestos-related disease (ARD) in the family (Cohen's d=0.41, 0.57). Survey 2 also found more positive attitudes towards research when a family member had ARD (Cohen's d=0.48). CONCLUSIONS: Principal components analysis shows different dimensions of attitudes towards research engagement. The different dimensions are related to community members' desire to be invited to participate in research, awareness of past research in the community and having been screened or diagnosed with a health condition related to the Superfund contaminant.

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.

Quantile regression in environmental health: Early life lead exposure and end-of-grade exams.

Conditional means regression, including ordinary least squares (OLS), provides an incomplete picture of exposure-response relationships particularly if the primary interest resides in the tail ends of the distribution of the outcome. Quantile regression (QR) offers an alternative methodological approach in which the influence of independent covariates on the outcome can be specified at any location along the distribution of the outcome. We implemented QR to examine heterogeneity in the influence of early childhood lead exposure on reading and math standardized fourth grade tests. In children from two urban school districts (n=1,076), lead exposure was associated with an 18.00 point decrease (95% CI: -48.72, -3.32) at the 10th quantile of reading scores, and a 7.50 point decrease (95% CI: -15.58, 2.07) at the 90th quantile. Wald tests indicated significant heterogeneity of the coefficients across the distribution of quantiles. Math scores did not show heterogeneity of coefficients, but there was a significant difference in the lead effect at the 10th (ß=-17.00, 95% CI: -32.13, -3.27) versus 90th (ß=-4.50, 95% CI: -10.55, 4.50) quantiles. Our results indicate that lead exposure has a greater effect for children in the lower tail of exam scores, a result that is masked by conditional means approaches.

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.

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.