Biology subjects

Baratta, A. M.

Publications and source records attributed to Baratta, A. M..

3 recordsLinked to original sources

bioRxiv2023

Home-Cage Sipper Devices Reveal Age and Sex Differences in Ethanol Consumption Patterns

BackgroundAlcohol consumption and alcohol use disorder (AUD) are influenced by circadian rhythms. Alcohol-related behaviors and circadian rhythms differ with age and sex, but little preclinical research has compared circadian patterns of ethanol consumption across ages and sexes. Cost-effective tools are becoming widely available that could elucidate these patterns, including open-source, Arduino-based home-cage sipper devices. We hypothesized these devices would reveal age- and sex-specific patterns of ethanol and water consumption and ethanol-induced changes in overall fluid consumption rhythms. MethodsWe used Arduino-based home-cage sipper devices in a continuous-access two-bottle choice (2BC) paradigm with water and ethanol (10% v/v) for 14 days to measure drinking patterns of male and female adolescent (3-week), young adult (6-week), and mature adult (18-week) C57BL/6J mice. Grams per kilogram (g/kg) fluid consumption were manually recorded at the beginning of each dark cycle, while sipper devices continuously recorded drinking. ResultsManually collected 2BC data confirmed greater ethanol consumption in females of all age groups as well as stepwise decreases in total fluid consumption with age in ethanol-exposed females and in both sexes in the water-only groups. Correlations of manually recorded versus sipper count data were strong and significant for ethanol, but modest for water, suggesting fluid differences in drinking microstructure. Blood ethanol concentrations were significantly correlated with sipper data, indicating sipper devices accurately determine temporal ethanol consumption. Sipper devices uncovered subtle differences in circadian rhythms by age, group, and ethanol exposure, including minor phase advancement in ethanol consumption with age in females, but delay in males, as well as a female-specific phase delay and weaker amplitude in total fluid consumption across age groups with ethanol exposure. ConclusionsWe show these devices capture circadian patterns of ethanol drinking behavior that differ by age, sex, and ethanol exposure inaccessible by manual 2BC measurements alone. Future studies may examine older age groups and further dissect circadian drinking patterns by age and sex and their molecular mechanisms relevant to AUD pathogenesis.

neuroscience↗

bioRxiv2022

Reducing brain kynurenic acid synthesis precludes kynurenine-induced sleep disturbances

Patients with neurocognitive disorders often battle sleep disturbances. Kynurenic acid (KYNA) is a tryptophan metabolite of the kynurenine pathway implicated in the pathology of these illnesses. Modest increases in KYNA, an antagonist at glutamatergic and cholinergic receptors, result in cognitive impairments and sleep dysfunction. We explored the hypothesis that inhibition of the KYNA synthesizing enzyme, kynurenine aminotransferase II (KAT II), may alleviate sleep disturbances. At the start of the light phase, adult male and female Wistar rats received systemic injections of either i) vehicle, ii) kynurenine (100mg/kg; i.p.), iii) the KAT II inhibitor, PF-04859989 (30 mg/kg; s.c.), or iv) PF-04859989 and kynurenine in combination. Kynurenine and KYNA levels were evaluated in the plasma and brain. Separate animals were implanted with electroencephalogram (EEG) and electromyogram (EMG) telemetry devices to record polysomnography and evaluate vigilance states wake, rapid eye movement sleep (REMS) and non-REM sleep (NREMS) following each treatment. Kynurenine challenge increased brain KYNA and resulted in reduced REMS duration, NREMS delta power and sleep spindles. PF-04859989 reduced brain KYNA formation when given prior to kynurenine, prevented disturbances in REM sleep and sleep spindles, and enhanced NREM sleep. Our findings suggest that reducing KYNA in conditions where the kynurenine pathway is activated may serve as a potential strategy for improving sleep dynamics.

neuroscience↗

bioRxiv2022

Mechanical and Heat Hyperalgesia upon Withdrawal from Chronic Intermittent Ethanol Vapor depends on Sex, Exposure Duration and Blood Alcohol Concentration in Mice

Approximately half of patients with alcohol use disorder (AUD) report pain and this can be severe during withdrawal. However, many questions remain regarding the importance of sex, blood alcohol concentration (BAC), time course, and pain modality. To examine the impact of sex and BAC on the time course of the development of mechanical and heat hyperalgesia, we characterized a mouse model of Chronic Alcohol Withdrawal Induced Pain (CAWIP) in the presence or absence the alcohol dehydrogenase inhibitor, pyrazole. Male and female C57BL/6J mice underwent chronic intermittent ethanol vapor (CIEV) {+/-} pyrazole exposure for 4 weeks, 4 days/week to induce ethanol dependence. Hind paw sensitivity to the plantar application of mechanical (von Frey filaments) and radiant heat stimuli were measured during weekly observations at 1, 3, 5, 7, 24, and 48 hr after cessation of ethanol exposure. In the presence of pyrazole, males developed mechanical hyperalgesia after the first week of CIEV exposure, peaking at 48 hours after cessation of ethanol. By contrast, females did not develop mechanical hyperalgesia until the fourth week; this also required pyrazole and did not peak until 48 hours. Heat hyperalgesia was consistently observed only in females exposed to ethanol and pyrazole; this developed after the first weekly session and peaked at 1 hour. We conclude that CAWIP develops in a sex -, time -, and BAC - dependent manner in C57BL/6J mice.

animal behavior and cognition↗