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Item Comparison of Subjective Responses to Oral and Intravenous Alcohol Administration under Similar Systemic Exposures(Wiley, 2019) Plawecki, Martin H.; Durrani, A. M.; Boes, Julian; Wetherill, Leah; Kosobud, Ann; O'Connor, Sean; Ramchandani, V. A.; Psychiatry, School of MedicineObjective To test whether an individual's subjective responses to alcohol are similar when the breath alcohol concentration (BrAC) trajectory resulting from oral administration is matched by intravenous administration. Background Individuals perceive the effects of alcohol differently, and the variation is commonly used in research assessing the risk for developing an alcohol use disorder. Such research is supported by both oral and intravenous alcohol administration techniques, and any differences attributable to the route employed should be understood. Methods We conducted a 2‐session, within‐subject study in 44 young adult, healthy, non‐dependent drinkers (22 females and 22 males). In the first session, subjects ingested a dose of alcohol which was individually calculated, on the basis of total body water, to yield a peak BrAC near 80 mg/dl, and the resulting BrAC trajectory was recorded. A few days later, subjects received an intravenous alcohol infusion rate profile, pre‐computed to replicate each individual's oral alcohol BrAC trajectory. In both sessions, we assessed 4 subjective responses to alcohol: SEDATION, SIMULATION, INTOXICATION, and HIGH; at baseline and frequently for 4 hours. We compared the individuals’ baseline‐corrected responses at peak BrAC and at half‐peak BrAC on both the ascending and descending limbs. We also computed and compared Pearson‐product moment correlations of responses by route of administration, the Mellanby measure of acute adaptation to alcohol, and the area under the entire response curve for each subjective response. Results No significant differences in any measure could be attributed to the route of alcohol administration. Eleven of 12 response comparisons were significantly correlated across the routes of alcohol administration, with 9 surviving correction for multiple measures, as did the Mellanby effect and area under the response curve correlations. Conclusion The route of alcohol administration has a minimal effect on subjective responses to alcohol when an individual's BrAC exposure profiles are similar.Item Integrative "omic" analysis reveals distinctive cold responses in leaves and roots of strawberry, Fragaria × ananassa 'Korona'(Frontiers Media SA, 2015) Koehler, Gage; Rohloff, Jens; Wilson, Robert C.; Kopka, Joachim; Erban, Alexander; Winge, Per; Bones, Atle M.; Davik, Jahn; Alsheikh, Muath K.; Randall, Stephen K.; Department of Biology, School of ScienceTo assess underlying metabolic processes and regulatory mechanisms during cold exposure of strawberry, integrative "omic" approaches were applied to Fragaria × ananassa Duch. 'Korona.' Both root and leaf tissues were examined for responses to the cold acclimation processes. Levels of metabolites, proteins, and transcripts in tissues from plants grown at 18°C were compared to those following 1-10 days of cold (2°C) exposure. When leaves and roots were subjected to GC/TOF-MS-based metabolite profiling, about 160 compounds comprising mostly structurally annotated primary and secondary metabolites, were found. Overall, 'Korona' showed a modest increase of protective metabolites such as amino acids (aspartic acid, leucine, isoleucine, and valine), pentoses, phosphorylated and non-phosphorylated hexoses, and distinct compounds of the raffinose pathway (galactinol and raffinose). Distinctive responses were observed in roots and leaves. By 2DE proteomics a total of 845 spots were observed in leaves; 4.6% changed significantly in response to cold. Twenty-one proteins were identified, many of which were associated with general metabolism or photosynthesis. Transcript levels in leaves were determined by microarray, where dozens of cold associated transcripts were quantitatively characterized, and levels of several potential key contributors (e.g., the dehydrin COR47 and GADb) to cold tolerance were confirmed by qRT-PCR. Cold responses are placed within the existing knowledge base of low temperature-induced changes in plants, allowing an evaluation of the uniqueness or generality of Fragaria responses in photosynthetic tissues. Overall, the cold response characteristics of 'Korona' are consistent with a moderately cold tolerant plant.Item Selection for High Alcohol Preference Drinking in Mice Results in Heightened Sensitivity and Rapid Development of Acute Functional Tolerance to Alcohol’s Ataxic Effects(Wiley, 2013-02) Fritz, Brandon M.; Grahame, Nicholas J.; Boehm, Stephen L. II; Department of Psychology, School of ScienceSelection for High Alcohol Preference Drinking in Mice Results in Heightened Sensitivity and Rapid Development of Acute Functional Tolerance to Alcohol’s Ataxic Effects Brandon M. Fritz , Nicholas J. Grahame , and Stephen L. Boehm II Indiana Alcohol Research Center and Department of Psychology, Indiana University – Purdue University Indianapolis, Indianapolis, IN 46202 Abstract Propensity to develop acute functional (or within session) tolerance to alcohol (ethanol) may influence the amount of alcohol consumed, with higher drinking associated with greater acute functional tolerance (AFT). The goal of the current study was to assess this potential correlated response between alcohol preference and AFT in second and third replicate lines of mice selectively bred for high (HAP2&3) and low (LAP2&3) alcohol preference drinking. Male and female mice were tested for development of AFT on a static dowel task which requires that animals maintain balance on a wooden dowel in order to prevent falling. On test day, each mouse received one (1.75g/kg; Experiment 1) or two (1.75g/kg and 2.0g/kg; Experiment 2) injections of ethanol; an initial administration before being placed on the dowel and in Experiment 2, an additional administration after the first regain of balance on the dowel. Blood samples were taken immediately after loss of balance (when BECs were rising) and at recovery (during falling BECs) in Experiment 1, and after first and second recovery in Experiment 2. It was found that HAP mice fell from the dowel significantly earlier and at lower BECs than LAP mice following the initial injection of ethanol and were therefore more sensitive to its early effects. Furthermore, Experiment 1 detected significantly greater AFT development (BECfalling - BECrising) in HAP mice as compared to LAP mice which occurred within ~30 min, supporting our hypothesis. However, AFT was not different between lines in Experiment 2, indicating that ~30–60 min following alcohol administration, AFT development was similar in both lines. These data show that high alcohol drinking genetically associates with both high initial sensitivity and very early tolerance to the ataxic effects of ethanol.