Can direct pathway stimulation cause addiction-like changes in behavior?

直接通路刺激能否导致类似成瘾的行为变化？

• 批准号: 10011310
• 负责人: Alexxai V Kravitz
• 金额: $ 37.86万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10011310
• 关键词: Behavior; Behavioral; Biological Assay; Corpus striatum structure; Disease; Drug Addiction; Environment; Food; Future; Learning; Motivation; Mus; Neurons; Pathway interactions; Phenotype; Process; Psychological reinforcement; Stimulus; Taste Perception; Testing; Time; Training; Work; addiction; cell type; experience; food addiction; novel; optogenetics; therapeutic target; willingness

In this project, we will train mice to self-stimulate their direct pathway medium spiny neurons (dMSNs) using optogenetics. In prior work, we have found that mice find this behavior highly reinforcing. However, prior work gave mice at most 90 minutes of total training time. We plan to expand this by a factor of 100, giving the mice much more experience with this highly reinforcing behavior. We will examine behavioral changes in these mice, including assaying their motivation to receive stimulation, willingness to work for stimulation, and willingness to endure negative consequences to receive stimulation.

在这个项目中，我们将使用光遗传学训练小鼠以自刺激其直接途径中刺神经元（DMSN）。 在先前的工作中，我们发现小鼠发现这种行为高度加强。 但是，先前的工作最多可以给小鼠总训练时间。 我们计划将其扩大100倍，从而使老鼠具有这种高度加强的行为的更多经验。 我们将检查这些小鼠的行为变化，包括分析他们接受刺激的动机，愿意为刺激而工作的意愿以及愿意忍受接受刺激的负面后果。

项目成果

Persistent effects of obesity: a neuroplasticity hypothesis.

• DOI: 10.1111/nyas.13665
• 发表时间: 2018-09
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Matikainen-Ankney BA;Kravitz AV
• 通讯作者: Kravitz AV

Do Dopaminergic Impairments Underlie Physical Inactivity in People with Obesity?

• DOI: 10.3389/fnhum.2016.00514
• 发表时间: 2016-10-14
• 期刊: FRONTIERS IN HUMAN NEUROSCIENCE
• 影响因子: 2.9
• 作者: Kravitz, Alexxai V.;O'Neal, Timothy J.;Friend, Danielle M.
• 通讯作者: Friend, Danielle M.

Working together: basal ganglia pathways in action selection.

• DOI: 10.1016/j.tins.2014.04.004
• 发表时间: 2014-06
• 期刊: Trends in neurosciences
• 影响因子: 15.9
• 作者: Friend DM;Kravitz AV
• 通讯作者: Kravitz AV

Optogenetic and chemogenetic insights into the food addiction hypothesis.

• DOI: 10.3389/fnbeh.2014.00057
• 发表时间: 2014
• 期刊: Frontiers in behavioral neuroscience
• 影响因子: 3
• 作者: Krashes MJ;Kravitz AV
• 通讯作者: Kravitz AV