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:
- 金额:$ 24.9万
- 依托单位:
- 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:
- 关键词:AbstinenceAddressAmygdaloid structureAnimal ExperimentationAnimal ModelAnteriorAssociation LearningBehavioralDecision MakingDedicationsDrug AddictionDrug InteractionsEmploymentFamilyFoodFutureGoalsHomeHumanImmunohistochemistryIncubatedKnowledgeLabelLaboratory AnimalsLateralLearningMeasuresMedialMentorsMethamphetamineModelingMolecularMonkeysNational Institute of Drug AbuseNeuronsOutputPharmaceutical PreparationsPhasePostdoctoral FellowProceduresPublishingRattusRecombinant adeno-associated virus (rAAV)RelapseResearchRewardsRodentRoleSelf AdministrationSocial InteractionSocial isolationSomatostatinSystemTechniquesTestingTracerTrainingViraladdictionaustinawakecell typecravingdesigner receptors exclusively activated by designer drugsdrug cravingexperiencefollow-upgenetic manipulationhigh rewardin vivoinsightknock-downneuralnon-drugnovelpeerpost-doctoral trainingpreferencepreventprogramsprotective effectrecruitsmall hairpin RNAsocialsocial 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.
项目摘要
尽管大步了解成瘾的电路和分子机制,但治疗选择
保持不变。这种僵局至少部分是由于结构和预测性的局限性
动物成瘾模型的有效性,很少纳入社会因素。在人类和实验室中
动物,不利的社会互动和社会隔离促进毒品自我管理和救济,而
社会互动往往受到保护。我最近开发了一种在药物之间选择的RAT模型
和社会互动,并显示了后者对成瘾的深刻保护作用。我的研究
揭示了两个主要发现:(1)大鼠强烈宁愿进行社交互动而不是药物,以及(2)社会选择 -
诱发的自愿戒酒阻止甲基苯丙胺(甲基苯丙胺)渴望孵育。这种保护作用
与中央杏仁核外侧部分(CEL)中的PKCδ激活有关(通过双标记评估
带有PKCδ的FOS)。相反,在归乡强迫禁欲之后,渴望的孵化与
选择性募集CEL-合作蛋白(SOM)神经元。因此,该提议的目的是研究(1)
社会奖励对甲基苯丙胺孵化的受保护作用的基础的电路机制,(2)
社会互动与选择甲基甲基的神经编码机制。在K99阶段,我将
研究社会奖励对冰毒渴望孵化的受保护作用的CEL机制。这会
可以使用shrnas病毒构建体来选择性地敲低PKCδ或最近由我的SOM开发
合作者Messing博士。此外,在Schoenbaum博士(我的同事)的指导下,我将使用
单个单元记录,以调查对社会奖励而不是甲基苯丙胺的偏爱的神经底物。
由于其在关联学习和决策中的关键作用,我将重点关注轨道额皮质。
在R00阶段,我将使用我在博士后培训和K99期间学到的技术
阶段以进一步表征社会互动对孵化的保护作用的电路机制
渴望和毒品的选择。拟议的培训将使我能够开发未来的独立研究
计划旨在确定社会因素在药物成瘾中作用的基础机制。
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:
- 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:
- 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:
- 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:
- 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.
- DOI:10.3389/fnbeh.2022.907327
- 发表时间:2022
- 期刊:
- 影响因子:3
- 作者:
- 通讯作者:
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Marco Venniro其他文献
Marco Venniro的其他文献
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{{ truncateString('Marco Venniro', 18)}}的其他基金
Behavioral and neural mechanisms mediating social motivation in a rat model for ASD
自闭症大鼠模型中调节社会动机的行为和神经机制
- 批准号:
10553444 - 财政年份:2022
- 资助金额:
$ 24.9万 - 项目类别:
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
- 批准号:
10407078 - 财政年份:2021
- 资助金额:
$ 24.9万 - 项目类别:
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
- 批准号:
10355849 - 财政年份:2021
- 资助金额:
$ 24.9万 - 项目类别:
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