Browsing by Author "Brunetti, Kaylee"
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Item Cocaine Administration but Not Morphine Leads to Increases in Impulsivity as Measured in a Delay Discounting Task(2024-03-21) Keitzer, Jeri; Anchondo, Olivia; Brunetti, Kaylee; Shuchi, Samia; Colon-Perez, LuisCocaine Administration but Not Morphine Leads to Increases in Impulsivity as Measured in a Delay Discounting Task Jeri Keitzer, Olivia Anchondo, Kaylee Brunetti, Samia Shuchi, and Luis Colon-Perez Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, 76107 Purpose: Inhibitory and cognitive control are mental process susceptible to repeated exposure to drugs of abuse. Specifically, impulsivity refers to the tendency to act prematurely without regard of the future. Substance use disorders patients (SUD) show impaired impulsivity; however, it is unclear whether psychostimulant use precedes impulsive behavior or vice versa. The delay discounting task is an assessment of impulsive choice used in behavioral neuroscience research. In this task, subjects are given a choice between an immediate small reward or a delayed large reward in which the time of delay increases across trials. Subjects that discount the delayed reward earlier are determined to act with more impulsivity. In this current study, we looked at impulsivity as it relates to performance in a delay discounting task before and after IP injection drug administration of either morphine or cocaine. We hypothesized that the subjects that were administered drugs would devalue the delayed reward earlier within the delay discounting task than control subjects. Methods: For this study, we used Sprague Dawley rats split into 4 different groups: cocaine, morphine, saline, and naïve. All subjects were food restricted to increase motivation to obtain the reward food pellets. Rats began training on the delay discounting task after a training phase in which the rats were introduced to the behavioral chambers and exposed to the levers within the chambers in which they were trained to press to receive pellets. The delay discounting task consisted of a daily session in which the subject went through 5 phases (a total of 60 total trials) choosing between two levers to receive pellets. Each phase is characterized by two forced trials and ten choice trials. In the forced choice trials, the animal has only one option: either the immediate small reward or delayed choice reward. At each phase the delay increases from no delay to 4s, 8s, 16s, and 32s. During choice trials, rats choose between the immediate and delayed levers. Once a decision has been made, both levers retract until the next trial. First, baseline data of each subject’s impulsive choice was acquired, then the subjects underwent IP injection of either cocaine, morphine, or saline. A naïve group did not receive any injections. Rats were injected with drugs according to their weight (5 mg/kg) once per day for seven days, then they completed the delay discounting task again under experimental conditions. Results: The cocaine drug group showed a significant decrease in delayed lever presses compared to all other groups during the delay discounting task following drug administration. No other significant differences were seen across any of the other groups. Conclusion: The results of the study suggest that passive administration of cocaine in rats may lead to an increase in impulsivity but not morphine.Item Neuroinflammation and gut diversity effects due to opioid self-administration(2024-03-21) Brunetti, Kaylee; Shuchi, Samia; Colon-Perez, LuisPurpose: Opioids are a great resource to treat pain in humans, but prolonged use can lead users to physical dependence and opioid use disorders (OUD). The use of opioids increases the risk of developing OUDs in humans via activation ofμ-opioid receptors. OUD is extensively studied for its effects in the central nervous system including the brain; however, Gut-Brain Axis (GBA) research will potentially expand our understanding of addiction and provide a new paradigm for developing new substance use disorder (SUD) therapeutics. GBA in animal models of OUDs can elucidate the complex interactions between the brain and gut that lead to pathological drug seeking and consumption and their relation to GBA components (i.e., bacterial populations, gut peptides, and gut signaling). In this study, we will share the determining temporal hallmarks of gut alterations in rats self-administering morphine for 15 days and relate it to neuroinflammatory features in the brain. One of our hypotheses is that abuse of drugs, such as morphine, starts by inducing inflammation of the brain and gut taxonomic changes similar to those observed in human opioid users. Methods: In this project, we used Sprague Dawley (SD) rats, and both the experimental and control groups were surgically implanted with intravenous (IV) catheters. The control group was exposed to the self-administration box, but only received sucrose pellets instead of morphine to avoid differences in behavior due to instrument learning or exposure to self-administration chambers. The experimental group was trained to self-administer morphine dosed to their body weight of 0.4 mg/kg for 14 days. The experimental timeline was (1) baseline: 7 days after catheter implantation, (2) acute: 24 hours after the second day of self-administration, and (3) chronic: 24 hours after completion of the 12 days of self-administration. Fecal samples were acquired at the three-time points and analyzed with 16s DNA sequencing to determine the relative abundance of microbial species at the time points. After the last day, we collected the brains from all animals and prepared tissue FFPE for immunohistochemistry and spatial transcriptomics analysis. Concurrently we acquired MRI diffusion-weighted scans in a 7.0 T preclinical scanner. Rats were restrained under sedation (isoflurane 5% induction, 2% maintenance) reducing the stressor of noise and restriction while scanning. This project will help us identify whether neuroinflammation markers occur due to large doses of morphine repetitively in rodents. Results: Preliminary analysis points out that chronic and voluntary administration of morphine leads to a neuroinflammatory response in the habenula possibly detected with diffusion MRI. Our preliminary16s DNA sequencing analysis has shown some key microbiome differences in our experimental drug group versus our control pellet group. Conclusion: As we continue analyzing our data, we hope to provide more insight on early effects of chronic drug use on gut-brain axis.