The protective effect of volitional social interaction on drug addiction

自愿社交互动对药物成瘾的保护作用

基本信息

批准号：
10615106
负责人：
Marco Venniro
金额：
$ 24.9万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10615106
关键词：
Abstinence Address Amygdaloid structure Animal Experimentation Animal Model Anterior Association Learning Behavioral Decision Making Dedications Drug Addiction Drug Interactions Employment Family Food Future Goals Home Human Immunohistochemistry Incubated Knowledge Label Laboratory Animals Lateral Learning Measures Medial Mentors Methamphetamine Modeling Molecular Monkeys National Institute of Drug Abuse Neurons Output Pharmaceutical Preparations Phase Postdoctoral Fellow Procedures Publishing Rattus Recombinant adeno-associated virus (rAAV)Relapse Research Rewards Rodent Role Self Administration Social Interaction Social isolation Somatostatin System Techniques Testing Tracer Training Viral addiction austin awake cell type craving designer receptors exclusively activated by designer drugs drug craving experience follow-up genetic manipulation high reward in vivo insight knock-down neural non-drug novel peer post-doctoral training preference prevent programs protective effect recruit small hairpin RNA social social factors

项目摘要

Project Summary Despite strides towards understanding circuit and molecular mechanisms of addiction, treatment options remain largely unchanged. This impasse is at least partly due to limitations in the construct and predictive validity of animal models of addiction, which rarely incorporate social factors. In both humans and laboratory animals, adverse social interactions and social isolation promote drug self-administration and relapse, while social interactions tend to be protective. I recently developed an operant rat model of choice between drugs and social interaction and showed the profound protective effects of the latter on addiction. My research revealed two major findings: (1) rats strongly prefer operant social interaction over drugs, and (2) social choice- induced voluntary abstinence prevents incubation of methamphetamine (Meth) craving. This protective effect was associated with activation of PKCδ in central amygdala lateral part (CeL) (assessed by double-labeling of Fos with PKCδ). In contrast, after homecage forced abstinence, incubation of craving was associated with selective recruitment of CeL-somatostatin (SOM) neurons. Therefore, the aim of this proposal is to study (1) the circuit mechanisms underlying the protective effect of social reward on incubation of Meth craving, and (2) the neural encoding mechanisms of the social interaction versus Meth choice. During the K99 phase, I will investigate a CeL mechanism of the protective effect of social reward on incubation of Meth craving. This will be achieved using shRNAs viral constructs to selectively knockdown PKCδ or SOM recently developed by my collaborator Dr. Messing. Additionally, under the guidance of Dr. Schoenbaum (my co-mentor), I will use single-unit recording to investigate the neural substrates underlying the preference for social reward over Meth. I will focus on the orbitofrontal cortex because of its critical role in associative learning and decision-making. During the R00 phase, I will use the techniques I have learned during my post-doctoral training and the K99 phase to further characterize the circuit mechanisms of the protective effect of social interaction on incubation of drug craving and drug choice. The proposed training will allow me to develop a future independent research program geared towards identifying mechanisms underlying the role of social factors in drug addiction.

项目概要尽管在理解成瘾的回路和分子机制方面取得了进展，但治疗方案这种僵局基本上没有改变，至少部分是由于结构和预测方面的限制。成瘾动物模型的有效性，很少在人类和实验室中纳入社会因素。动物、不良的社会互动和社会隔离会促进药物的自我给药和复发，而我最近开发了一种药物选择的操作性大鼠模型。我的研究显示了后者对成瘾的深远保护作用。揭示了两个主要发现：（1）老鼠强烈喜欢操作性的社会互动而不是药物，（2）社会选择- 诱导性自愿戒断可防止对甲基苯丙胺 (Meth) 的渴望产生这种保护作用。与中央杏仁核外侧部分 (CeL) 的 PKCδ 激活相关（通过双标记评估） Fos 与 PKCδ）相反，在家笼强制禁欲后，渴望的孵化与相关。因此，本提案的目的是研究 (1)。社会奖励对冰毒渴望产生保护作用的循环机制，以及（2）在 K99 阶段，我将讨论社交互动与冰毒选择的神经编码机制。研究社会奖励对冰毒渴望孵化的保护作用的 CeL 机制。使用 shRNA 病毒构建体选择性敲低 PKCδ 或 SOM 来实现，这是我最近开发的另外，在Schoenbaum博士（我的合作导师）的指导下，我将使用Messing博士的合作者。单单元记录来研究社会奖励优于冰毒的神经基础。我将重点关注眶额皮层，因为它在联想学习和决策中发挥着关键作用。在R00阶段，我将使用我在博士后培训期间学到的技术和K99 阶段进一步表征社会互动对孵化的保护作用的循环机制拟议的培训将使我能够开展未来的独立研究。旨在确定社会因素在吸毒成瘾中的作用的潜在机制的计划。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Waving Through the Window: A Model of Volitional Social Interaction in Female Mice.

DOI：
10.1016/j.biopsych.2021.10.023
发表时间：
2022-06-01
期刊：
Biological psychiatry
影响因子：
10.6
作者：
通讯作者：

Increased heroin intake and relapse vulnerability in intermittent relative to continuous self-administration: Sex differences in rats.

DOI：
10.1111/bph.15791
发表时间：
2023-04
期刊：
British journal of pharmacology
影响因子：
7.3
作者：
通讯作者：

Calcitonin receptor signal: a potential target for opioid use disorder?

降钙素受体信号：阿片类药物使用障碍的潜在目标？

DOI：
10.1038/s41386-023-01702-4
发表时间：
2023
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
0
作者：
Marino,RosaAM;Venniro,Marco
通讯作者：
Venniro,Marco

Factors modulating the incubation of drug and non-drug craving and their clinical implications.

DOI：
10.1016/j.neubiorev.2021.09.050
发表时间：
2021-12
期刊：
Neuroscience and biobehavioral reviews
影响因子：
8.2
作者：
Venniro M;Reverte I;Ramsey LA;Papastrat KM;D'Ottavio G;Milella MS;Li X;Grimm JW;Caprioli D
通讯作者：
Caprioli D

Editorial: The Double Facets of Social Behavior in Drug Addiction.