Browsing by Subject "rat"

Now showing 1 - 3 of 3
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    Defining the pharmacology of sustained-release buprenorphine in acute and chronic pain states in various species
    (2021-12) Larson, Christina
    Pain is a clinical syndrome arising from a variety of etiologies, which creates difficulty in successfully treating the individual patient. Sustained-release buprenorphine is widely used in a variety of species with the intention of providing long-lasting analgesia. Statements about duration of therapeutic efficacy are based on persistence of serum buprenorphine levels over a minimum threshold, but behavioral data demonstrating sustained efficacy is not established. Additionally, chronic opioid exposure can induce tolerance and/or hyperalgesia; many species receiving sustained-release buprenorphine have not been evaluated for these effects.This work reviews buprenorphine metabolism, opioid signaling, and pain models to establish the context for examining the clinical efficacy and duration of analgesia provided by a single subcutaneous administration of sustained-release buprenorphine at clinically-recommended doses in mice, rats, and cats under conditions of inflammatory pain (mice and rats), cancer pain (mice), thermal nociception (mice and rats), and post-operative pain (mice, rats, and cats). Mice and rats were also screened for development of opioid tolerance. In mice and rats, a single subcutaneous administration of sustained-release buprenorphine produced analgesia for hours rather than days, and subsequent administration of buprenorphine produced a decreased dose-response curve. In cats, ketoprofen offered as much or more analgesia after ovariohysterectomy under multi-modal anesthesia as sustained-release buprenorphine does, when assessed by spontaneous behavioral measures and by evoked reflexive measures. Based on assessments using evoked reflexive measurements in mice and rats, there is evidence that a single subcutaneous administration of sustained-release buprenorphine at clinically-recommended doses induces acute opioid tolerance in mice and rats, shortening the duration of antinociception. It is reasonable to suspect that a similar mechanism may occur in the cat leading to decreased analgesic efficacy in the post-operative period.
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    Information Processing in the Orbitofrontal Cortex and the Ventral Striatum in Rats Performing an Economic Decision-Making Task
    (2015-08) Stott, Jeffrey
    The orbitofrontal cortex (OFC) and ventral striatum (vStr) are key brain structures that represent information about value during decision-making tasks. Despite their very different anatomical properties, numerous studies have found similar patterns of value-related signaling in these structures. In particular, both structures are intimately involved in delay-discounting tasks, which involve a tradeoff between reward magnitude and delay to reward. However, the overlapping activity profiles of these brain regions makes it difficult to tease apart their specific contributions to delay-discounting behavior, and to economic decision-making more generally. In order to better understand the contributions of these two regions to value-based choice, we made simultaneous recordings in the OFC and vStr in rats performing a spatial variant of a traditional delay-discounting task. This allowed us to compare OFC and vStr activity directly in the same subjects while they engaged in a prototypical economic decision-making task, and additionally it allowed us to leverage the tools of spatial decoding analysis to measure non-local reward signaling. Chapter 1 provides an introduction to current theories of OFC and vStr function within the decision-making literature, in particular contrasting the concepts of neuroeconomics with the multiple decision-making systems framework. Chapter 2 describes the methods used in this thesis, including the design of the spatial delay-discounting task and the analysis of the neural data. Chapter 3 presents the results of single-unit and Bayesian decoding analyses from this dataset. We found that activity in the OFC and vStr was quite similar at the single-unit level, and inconsistent with the neuroeconomic account of value signaling in a common currency. Instead, when we looked specifically at moments of deliberative decision-making (as emphasized by the multiple systems account), we found important differences between the OFC and vStr. Both the OFC and the vStr showed covert reward signaling during deliberative, vicarious trial-and-error (VTE) behaviors. But vStr signals emerged earlier, before the moment of choice, while covert reward coding in the OFC appeared after the rats had committed to their decision. These analyses were extended to the level of local field potentials (LFPs), recorded from the same dataset. Local field potentials are a useful tool for studying local processing and interactions between brain regions. Chapter 4 describes the LFP results. Important among these was the finding that the vStr led the OFC at the LFP level (again showing temporal precedence), and furthermore, that the vStr was a stronger driver of OFC activity than vice versa, particularly during VTE. The implications of these results, along with those from the single-unit and Bayesian decoding analyses, are discussed in Chapter 5. Emphasis is placed on our emerging understanding of the role of the vStr in flexible behavior, and how the OFC and the vStr might cooperate to influence value-based choice.
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    Multiscale Investigation of Low Intensity Transcranial Focused Ultrasound Neuromodulation in in-vivo Rodent Models
    (2017-12) Niu, Xiaodan
    Transcranial focused ultrasound (tFUS) is a noninvasive neuromodulation method that modulates neural activity using mechanical pressure waves. tFUS has emerged as a promising noninvasive neuromodulation method with millimeter scale resolution and propensity to stimulate deep structures. Researchers have reported tFUS induced short term excitation or inhibition at cortical or deep brain. Currently, there are no reports of long term effects elicited by tFUS. The ability to use tFUS to non-invasively induce long term changes in the brain expands the clinical utility of tFUS. In order to explore the long term effects of tFUS on synaptic connectivity, we first evaluated our setup by examining the ability of tFUS to reliably induce short term changes to in vivo rats. After establishing our setup, we applied pulsed ultrasound to encode temporal information into the hippocampus to induce long term depression in 5 adult rats. Further investigations are needed to explore the underlying mechanisms.