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Cortical and Subthalamic Circuits in the Regulation of Addiction-like Behaviors
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Cortical and Subthalamic Circuits in the Regulation of Addiction-like Behaviors. |
| 개인저자 | Nakata, Kanichi G. |
| 단체저자명 | University of Washington. Neuroscience. |
| 발행사항 | [S.l.]: University of Washington., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 105 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-03B. Dissertation Abstract International |
| ISBN | 9781085730761 |
| 학위논문주기 | Thesis (Ph.D.)--University of Washington, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Advisor: Ferguson, Susan M. |
| 이용제한사항 | This item must not be sold to any third party vendors.This item must not be added to any third party search indexes. |
| 요약 | Addiction is a debilitating and complex neuropsychiatric disorder that generates substantial medical, social, monetary, and emotional costs for both addicted individuals and society. In spite of these costs, relapse rates remain high and effective interventions lacking, attributable in part to our limited understanding of the complex pathophysiology and neural substrates underlying addiction. The corticolimbic circuitry which underlies many of the maladaptive behaviors associated with addiction is a complex and interwoven network. Under normal conditions, this network helps regulate a wide array of motor, associative, and affective behaviors, allowing us to shape our actions adaptively in response to environmental rewards, dangers, and other stimuli. However, the use of addictive drugs initiates a broad cascade of intra- and extracellular changes to this circuitry, which are believed to underlie the transition from controlled, volitional drug use to the uncontrolled, compulsive drug abuse that defines addiction. The interconnectivity of addiction circuitry presents a significant challenge for studies seeking to explore how addiction emerges from drug-induced neuroadaptations, but recent advances in virus-mediated chemogenetic manipulation have allowed targeted examination of discrete neuronal circuits in ways not previously possible, allowing us to examine how specific components of the corticolimbic network contribute to drug addiction.The overarching goal of this dissertation was to leverage chemogenetic tools to investigate how corticostriatal and subthalamic circuits, critical components of the corticolimbic network, regulate addiction-like behaviors in rodents, including locomotor sensitization to amphetamine as well as self-administration and seeking of cocaine. The first chapter establishes the current state of knowledge surrounding cortical and subthalamic involvement in drug addiction. The second chapter demonstrates how inhibition of neuronal projections from medial prefrontal cortex to the nucleus accumbens transiently attenuates the development of amphetamine sensitization while also enhancing conditioned responding to drug-associated cues, slowing extinction of cocaine self-administration, and enhancing drug-primed reinstatement of drug seeking. The third chapter describes how stimulation of the subthalamic nucleus dramatically blocks the development of amphetamine sensitization, while inhibition only transiently enhances induction of sensitization. It also describes how inhibition of subthalamic afferents from the ventral pallidum and prelimbic cortex both attenuate conditioned responding to drug-associated procedures, with only the prelimbic projection significantly attenuating the persistence of sensitization and neither altering its induction, suggesting a complex role for the subthalamic nucleus in larger addiction circuitry. |
| 일반주제명 | Neurosciences. Health sciences. Psychobiology. |
| 언어 | 영어 |
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