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An Examination of Goal-Directed Moti...
~
Columbia University.
An Examination of Goal-Directed Motivation in Mice : = The Role of Dopamine D2 and Serotonin 2C Receptors.
紀錄類型:
書目-語言資料,手稿 : Monograph/item
正題名/作者:
An Examination of Goal-Directed Motivation in Mice :/
其他題名:
The Role of Dopamine D2 and Serotonin 2C Receptors.
作者:
Bailey, Matthew R.
面頁冊數:
1 online resource (273 pages)
附註:
Source: Dissertation Abstracts International, Volume: 78-12(E), Section: B.
Contained By:
Dissertation Abstracts International78-12B(E).
標題:
Neurosciences. -
電子資源:
click for full text (PQDT)
ISBN:
9780355083064
An Examination of Goal-Directed Motivation in Mice : = The Role of Dopamine D2 and Serotonin 2C Receptors.
Bailey, Matthew R.
An Examination of Goal-Directed Motivation in Mice :
The Role of Dopamine D2 and Serotonin 2C Receptors. - 1 online resource (273 pages)
Source: Dissertation Abstracts International, Volume: 78-12(E), Section: B.
Thesis (Ph.D.)--Columbia University, 2017.
Includes bibliographical references
Motivation has been defined as a set of processes which enables organisms to overcome obstacles by energizing behavior in the pursuit of a goal. There are several important observations about motivated behavior which provide insight into the neural mechanisms underlying goal-directed motivation. First, motivation serves two important functions, as it both energizes behavior and also directs it toward or away from specific stimuli. Many of the behavioral tasks used to assay motivation in laboratory rodents do not specifically aim to measure these two distinct aspects of motivation. A second feature of goal-directed motivation is that it is sensitive to both costs and benefits of a given situation, enabling animals to make cost-benefit decisions. Again, many of the behavioral tasks which study cost-benefit decision making do not specifically aim to independently measure the impact of cost manipulations and benefit manipulations in an isolated manner. Here, I first develop behavioral measures which aim to specifically dissociate activational and directional effects of motivation. By characterizing a novel behavioral measure known as a Progressive Hold Down (PHD) task, and using this task in parallel with a more traditionally used Progressive Ratio (PR) task, I show that methamphetamine robustly enhances activational effects of motivation, leading to increased response rates in both the PHD and PR task, but mice are not more goal-directed in the PHD task. I next develop and characterize two novel behavioral assays which are specifically used to examine effort and value contributions to cost-benefit decision making. The Concurrent Effort Choice (CEC) task measures how changes in effort levels impact decision making whereas the Concurrent Value Choice (CVC) task measure how changes in reward value impact decision making. Using these novel assays to examine specific processes important for goal-directed motivation, I carefully examine the role of manipulation of the Dopamine D2 receptor (D2R) in a mouse model which over-expresses the D2R within the striatum (D2R-OE), and the role of pharmacological manipulation of the Serotonin 2C receptor (5-HT2CR) with the functionally selective ligand SB242084. Whereas D2R-OE specifically impacts sensitivity to changes in effort levels which decrease overall levels of goal-directed motivation, selective modulation of the 5-HT2CR via treatment with SB242084 increases response vigor through enhanced dopamine release in the dorsomedial striatum, but this increase in response vigor does not alter sensitivity to effort or value changes when working for rewards. Together, these studies demonstrate the benefits of developing a more nuanced understanding of how specific manipulations impact motivated behavior by examining the specific underlying processes being altered.
Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018
Mode of access: World Wide Web
ISBN: 9780355083064Subjects--Topical Terms:
593561
Neurosciences.
Index Terms--Genre/Form:
554714
Electronic books.
An Examination of Goal-Directed Motivation in Mice : = The Role of Dopamine D2 and Serotonin 2C Receptors.
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Motivation has been defined as a set of processes which enables organisms to overcome obstacles by energizing behavior in the pursuit of a goal. There are several important observations about motivated behavior which provide insight into the neural mechanisms underlying goal-directed motivation. First, motivation serves two important functions, as it both energizes behavior and also directs it toward or away from specific stimuli. Many of the behavioral tasks used to assay motivation in laboratory rodents do not specifically aim to measure these two distinct aspects of motivation. A second feature of goal-directed motivation is that it is sensitive to both costs and benefits of a given situation, enabling animals to make cost-benefit decisions. Again, many of the behavioral tasks which study cost-benefit decision making do not specifically aim to independently measure the impact of cost manipulations and benefit manipulations in an isolated manner. Here, I first develop behavioral measures which aim to specifically dissociate activational and directional effects of motivation. By characterizing a novel behavioral measure known as a Progressive Hold Down (PHD) task, and using this task in parallel with a more traditionally used Progressive Ratio (PR) task, I show that methamphetamine robustly enhances activational effects of motivation, leading to increased response rates in both the PHD and PR task, but mice are not more goal-directed in the PHD task. I next develop and characterize two novel behavioral assays which are specifically used to examine effort and value contributions to cost-benefit decision making. The Concurrent Effort Choice (CEC) task measures how changes in effort levels impact decision making whereas the Concurrent Value Choice (CVC) task measure how changes in reward value impact decision making. Using these novel assays to examine specific processes important for goal-directed motivation, I carefully examine the role of manipulation of the Dopamine D2 receptor (D2R) in a mouse model which over-expresses the D2R within the striatum (D2R-OE), and the role of pharmacological manipulation of the Serotonin 2C receptor (5-HT2CR) with the functionally selective ligand SB242084. Whereas D2R-OE specifically impacts sensitivity to changes in effort levels which decrease overall levels of goal-directed motivation, selective modulation of the 5-HT2CR via treatment with SB242084 increases response vigor through enhanced dopamine release in the dorsomedial striatum, but this increase in response vigor does not alter sensitivity to effort or value changes when working for rewards. Together, these studies demonstrate the benefits of developing a more nuanced understanding of how specific manipulations impact motivated behavior by examining the specific underlying processes being altered.
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