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Browsing by Subject "Reward"

Now showing 1 - 3 of 3
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    A Dual Investigation of Questions in Drug Addiction: Exploring the Role of Neuroinflammation in Opioid Withdrawal and A Novel Measure of Reward-Seeking Behavior in Rodents
    (2016-08) Kennedy, Bruce
    Substance abuse disorders are extremely disruptive to the lives and relationships of those who suffer from them and are a burden on society and the healthcare system. Effective treatments are currently lacking and our understanding of the neurobiology driving addictive behaviors remains incomplete. The following animal studies aimed to advance the drug addiction field by 1) investigating neuroimmune interactions as a potential mechanism in opioid withdrawal in mice as well as 2) introducing a novel behavioral test in order to expand the repertoire of tools available to researchers investigating drug or reward-seeking behaviors in rats. Microglia, the immune cells of the brain have been recently recognized as being important contributors in a wide variety of neuropsychiatric disorders, including drug addiction. Although current views support a microglia role in the physical drug dependence experienced by opioids addicts, it is thought that the emotional effects of withdrawal, such as anxiety and depression, are better predictors of relapse. In the first series of experiment, a genetic mouse model lacking the key microglia immune receptor TLR4 was used to determine the involvement of this protein in the molecular and behavioral responses to opioid withdrawal, in particular those related to negative emotions. Although technological advances in behavioral testing techniques have improved our ability to model drug addiction in rodents, the low-tech behavioral assays used most frequently have remained largely unchanged over the last several decades. The second set of experiments introduced and validated a novel behavioral task based on the classic measure of reward, conditioned place preference. In the modified test, objects rather than contexts were used as a conditioned cue, which potentially allows for greater flexibility and opens up new ways of analyzing conditioned approach, a commonly used measure for assessing the reward value of a given substance.
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    Investigation of Glutamatergic Circuitry Underlying Copulatory Reward in Female Syrian Hamsters
    (2019-01) Moore, Kelsey
    Sex behavior in female mammals is known to involve rewarding consequences that increase the motivation to copulate. I have utilized female hamsters as a model to examine the underlying circuitry and mechanisms of this natural reward. Despite a wealth of information detailing dopaminergic neurotransmission in this region during sexual behavior, the role of glutamate, although the major excitatory neurotransmitter in the brain, has been disproportionately understudied. The goal of this dissertation work was to help close this gap in knowledge to further develop an understanding of the complex underpinnings of female sexual reward and motivation. This understanding is vital in the effort towards evidence-based therapeutic targets in the treatment of disorders of sexual desire in women. In order to determine the role of glutamate in signaling the rewarding properties of sex, I utilized a multi-faceted approach. First, through establishing the use of enzymatic biosensing in the lab, I evaluated glutamate release patterning in key reward regions during sexual behavior in the female hamster. I discovered time-locked glutamate transients specifically in the core of the nucleus accumbens (NAc) in response to penile intromission from the male. Next, I sought to uncover the potential source of this glutamate innervation of the NAc. Immunohistochemical and retrograde tracing analyses determined the involvement of excitatory glutamatergic efferents from the medial prefrontal cortex (mPFC) to the NAc. Then, to determine if mPFC activity was driving the activation of the NAc during female sexual behavior, I employed designer receptors exclusively activated by designer drugs (DREADDs) to selectively inhibit these excitatory mPFC efferents. I demonstrated that this selective inhibition decreases sex-induced activation of the NAc, confirming the importance of the mPFC in driving increased glutamatergic activity in the NAc in response to sexual behavior in the female. The novel findings reported in this body of work demonstrate the involvement of glutamatergic neurotransmission in sexual reward through a prefrontal-accumbal circuit. These are not only exciting additions to the development of a comprehensive model of female sexual reward, but also provide potential targets for therapeutic intervention. Currently there are no effective treatment options for disorders of sexual desire in women and these results provide attractive avenues for pursuing target-specific and clinically-relevant therapies.
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    Towards a Translational Model of Decision-Making: Findings from the Web-Surf Task
    (2017-08) Abram, Samantha
    Interventions targeting cognitive disorders often hinge on assumptions that humans and nonhuman animals recruit equivalent cognitive mechanisms during decision- making. Identifying parallel decision systems across species could help bridge gaps between clinical and non-clinical research, and in turn, improve intervention efficacy. The goal of this dissertation is to assess for similar behavioral and neural markers of decision-making across humans and rodents using a sequential foraging paradigm (“The Web-Surf Task”) that was adapted from a rodent spatial neuroeconomic task (“Restaurant Row”). The included studies highlight a functional translational approach that aims to access similar functional constructs via parallel tasks and methodological approaches. The results provide evidence of cross-species behavioral equivalents, such as the ability to detect revealed preferences. Findings from a neuroimaging study suggest that different neural systems track past and forward representations, indicative of human prospection during deliberation (i.e., episodic future thinking). Moreover, neural activation related to difficult decisions is similar to many of the structures that underlie rodent deliberation. Lastly, a risk-variant of the task suggests that regret-instances provide a bridge between our liking and pursuit of rewards. This final study also finds that impulsive individuals may fail to learn from regret. Collectively, this dissertation demonstrates the utility of this novel task for elucidating human deliberative mechanisms and identifying cross-species decision system compatibilities.