Browsing by Subject "Sucrose"
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Item Achieving pharmacologically relevant IV alcohol self-administration in the rat(2012-09-27) Windisch, Kyle Allyson; Czachowski, Cristine L.; Grahame, Nicholas J.; Kosobud, Ann E. K.Alcohol consumption produces a complex array of effects that can be divided into two types: the explicit pharmacological effects of ethanol (which can be quite separate temporally from time of intake) and the more temporally “relevant” effects (primarily olfactory and taste) that bridge the time from intake to the onset of the pharmacological effects. Dissociating these effects is essential to untangling the neurologic underpinnings of alcohol abuse and dependence. Intravenous self-administration of ethanol allows for controlled and precise dosing, bypasses first order absorption kinetics allowing for a faster onset of pharmacologic effects, and eliminates the confounding “non-pharmacological” effects associated with oral consumption. Intravenous self-administration of ethanol has been reliably demonstrated in both mouse and human experimental models; however, consistent intravenous self-administration of pharmacologically relevant levels of ethanol remains elusive in the rat. Previous work has demonstrated reliable elevated intravenous ethanol self administration using a compound reinforcer of oral sucrose and intravenous ethanol. The present study sought to elucidate the role of each component of this reinforcer complex using a multiple schedule study design. Male P rats had free access to both food and water during all intravenous self-administration sessions and all testing was performed in conjunction with the onset of the dark cycle. Once animals achieved stable operant responding on both levers for an orally delivered 1% sucrose solution (1S) on a FR4 schedule, surgery was conducted to implant an indwelling jugular catheter. Animals were habituated to the attachment of infusion apparatus and received twice daily sessions for four days to condition each lever to its associated schedule. Animals were then trained to respond on a multiple FR4-FR4 schedule composed of alternating 2.5 minute components. During one component only oral 1S was presented, while in the second component a compound reinforcer of oral 1S + IV 20% ethanol was presented (25 mg/kg/injection). Both levers were extended into the chamber during the session, with the active lever/schedule alternating as the session progressed across components. Average ethanol intake was 0.47 ± 0.04 g/kg. A significant increase in sucrose only reinforcers and sucrose lever error responding was found suggesting that sucrose not ethanol is responsible for driving overall responding. The current findings suggest that the existing intravenous ethanol self-administration methodology remains aversive in the rat.Item Brain Responses to Sugar: Implications for Alcohol Use Disorder and Obesity(2024-05) Alessi, Jonathan P.; Yoder, Karmen K.; Kareken, David A.; Džemidžić, Mario; Considine, Robert V.; Harezlak, JaroslawObesity and alcohol use may together account for 640,000 adult deaths each year in the United States. In both cases, overconsumption drives untoward effects. Alcohol use and obesity also both relate to sweet liking, as sugar consumption is consistently linked to weight gain and intense sweet liking has been linked to an inherited risk for alcohol use disorder (AUD). However, the neural underpinnings of these associations are largely unknown. Thus, we used sugar-sweetened water administration during functional magnetic resonance imaging (fMRI) to probe these relationships in two studies. In the first, we tested the relationship between a known AUD risk factor, subjective response to alcohol, and the brain response to both sucrose and monetary reward in 140 young adults. We found a significant positive correlation between the enjoyable component of subjective responses to a standardized intravenous alcohol exposure and activation to high-concentration sucrose (but not monetary reward) in the right dorsal anterior insula and the supplementary motor area, supporting a role for these regions in AUD risk. In the second study, we investigated the neural mechanisms of sweet liking decreases following bariatric surgery, the most effective obesity treatment. Here, we evaluated the change in brain activation to sucrose in 24 women before (BMI 47.0 + 6.9 kg/m2) and 21 women after (BMI 37.6 + 6.5 kg/m2) bariatric surgery and compared the pre- and post-surgical activation patterns to those of 21 normal to overweight (BMI 23.5 + 2.5 kg/m2) control participants. Brain activation did not differ between controls and surgery participants at either time point. However, activation to sucrose in reward, but not sensory, regions decreased significantly after surgery, consistent with reduced drive to consume sweet foods. Together, these studies highlight the utility of quantifying brain responses to sweet taste as a method to understand the mechanisms underlying overconsumptive behavior.Item Comparative study of the modulation of fructose/sucrose-induced hepatic steatosis by mixed lipid formulations varying in unsaturated fatty acid content(Springer (Biomed Central Ltd.), 2015) Siddiqui, Rafat A.; Xu, Zhidong; Harvey, Kevin A.; Pavlina, Thomas M.; Becker, Michael J.; Zaloga, Gary P.; Department of Medicine, IU School of MedicineBACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries. NAFLD encompasses a spectrum of diseases, ranging from hepatic steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and liver failure. The etiology of NAFLD remains unclear but is thought to relate to increased fatty acid flux within the liver that results in toxic fatty acid metabolite production. One source of increased fatty acid flux is fructose/sucrose-induced hepatic lipogenesis. Current treatment for NAFLD encompasses dietary modifications. However, little scientific evidence exists on which to base many dietary recommendations, especially the intake of different types of carbohydrates and fats. We hypothesized that lipid mixtures of unsaturated fatty acids would inhibit lipogenesis and subsequent hepatic steatosis induced by high carbohydrate diets. The aim of this study was to examine the effects of different complex mixtures of fatty acids upon the development of fructose/sucrose-induced hepatic steatosis. METHODS: C57BL/6 mice were randomized to normocaloric chow-based diets that varied in the type of carbohydrate (starch, sucrose, fructose). Animals in each carbohydrate group were further randomized to diets that varied in lipid type (no additional lipid, soybean oil, fish oil, olive/soybean oil, macadamia nut oil). These oils were chosen based upon their content of omega-6 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, omega-9 monounsaturated fatty acids, or omega-7 monounsaturated fatty acids. Fatty acid flux in the liver was determine by assessing hepatic lipid content (steatosis). We also assessed fatty acid levels in the plasma and liver of the animals, hepatic lipogenesis activity, hepatic stearoyl-CoA-1 desaturase activity, and hepatic elongase activity. RESULTS: Animals consumed similar amounts of the diets and maintained normal body weights throughout the study. Both sucrose and fructose induced hepatic lipogenesis and steatosis, with fructose being more potent. All mixed lipids similarly inhibited steatosis, limiting lipid content to levels found in the control (starch) animals. Lipogenesis and stearoyl-CoA-1 desaturase activity were increased in the sucrose and fructose groups. Levels of these enzymatic processes remained at baseline in all of the lipid groups. CONCLUSION: This is the first study to compare various complex lipid mixtures, based upon dietary oils with different types of long-chain fatty acids, upon development of sucrose/fructose-induced steatosis. Both carbohydrate source and lipid content appear important for the modulation of steatosis. Moderate intake of complex lipids with high unsaturated to saturated fatty acid ratios inhibited both lipogenesis and steatosis.Item Correction: High-intensity sweet taste as a predictor of subjective alcohol responses to the ascending limb of an intravenous alcohol prime: an fMRI study(Springer Nature, 2024) Alessi, Jonathan; Dzemidzic, Mario; Benson, Katherine; Chittum, George; Kosobud, Ann; Harezlak, Jaroslaw; Plawecki, Martin H.; O’Connor, Sean J.; Kareken, David A.; Neurology, School of MedicineCorrection to: Neuropsychopharmacology 10.1038/s41386-023-01684-3, published online 07 August 2023 The publication date for reference 21 was corrected from 2016 to 1977. The correct reference should read “Radloff LS. The CES-D Scale. Appl Psychol Meas. 1977;1:385–401”. The original article has been corrected.Item A preliminary study of the human brain response to oral sucrose and its association with recent drinking(Wiley Blackwell (Blackwell Publishing), 2013-12) Kareken, David A.; Dzemidzic, Mario; Oberlin, Brandon G.; Eiler, William J. A. II; Department of Neurology, IU School of MedicineBACKGROUND: A preference for sweet tastes has been repeatedly shown to be associated with alcohol preference in both animals and humans. In this study, we tested the extent to which recent drinking is related to blood oxygen level-dependent (BOLD) activation from an intensely sweet solution in orbitofrontal areas known to respond to primary rewards. METHODS: Sixteen right-handed, non-treatment-seeking, healthy volunteers (mean age: 26 years; 75% male) were recruited from the community. All underwent a taste test using a range of sucrose concentrations, as well as functional magnetic resonance imaging (fMRI) during pseudorandom, event-driven stimulation with water and a 0.83 M concentration of sucrose in water. RESULTS: [Sucrose > water] provoked a significant BOLD activation in primary gustatory cortex and amygdala, as well as in the right ventral striatum and in bilateral orbitofrontal cortex. Drinks/drinking day correlated significantly with the activation as extracted from the left orbital area (r = 0.52, p = 0.04 after correcting for a bilateral comparison). Using stepwise multiple regression, the addition of rated sucrose liking accounted for significantly more variance in drinks/drinking day than did left orbital activation alone (multiple R = 0.79, p = 0.002). CONCLUSIONS: Both the orbitofrontal response to an intensely sweet taste and rated liking of that taste accounted for significant variance in drinking behavior. The brain response to sweet tastes may be an important phenotype of alcoholism risk.