BDNF in the Reward Circuit for DBS-Induced Opioid Extinction
DBS 引起的阿片类药物灭绝的奖赏回路中的 BDNF
基本信息
- 批准号:10629686
- 负责人:
- 金额:$ 14.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-01 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:Amygdaloid structureAnimal ModelAnimalsAreaAttenuatedBehavioralBiologicalBrainBrain DiseasesBrain regionBrain-Derived Neurotrophic FactorCOVID-19 pandemicCessation of lifeCholera ToxinClinicClozapineCuesDataDeep Brain StimulationDorsalDrug ModelingsElectric StimulationExtinctionFrequenciesFutureGeneticGenetic TechniquesGlutamatesGrantHippocampusHumanImpairmentImplanted ElectrodesInjectionsKnowledgeLocationMeasuresMedialMemoryMental disordersMolecularMorphineMovement DisordersNeuronsNeurosurgical ProceduresNeurotrophic Tyrosine Kinase Receptor Type 2Nucleus AccumbensOpiate AddictionOpioidOverdoseOxidesPersonsPharmaceutical PreparationsPharmacological TreatmentPhasePhysiologic pulsePilot ProjectsPopulationPrefrontal CortexPrincipal InvestigatorProceduresProcessRattusRefractoryRelapseReportingResearchResearch PersonnelResearch Project GrantsResistanceRewardsRodentRodent ModelRoleSubstance Use DisorderTimeVentral Striatumaddictionantagonistcocaine overdoseconditioned place preferencecost estimatedesigner receptors exclusively activated by designer drugsdrug seeking behaviordrug testingexperimental studygenetic approachgenetic manipulationimmunoreactivityinsightlearning extinctionnervous system disorderopioid use disorderpharmacologicpreventprogramsreduce symptomsretrograde transportsobrietysuicidal morbiditytool
项目摘要
Abstract/Summary
Deep brain stimulation (DBS) is a neurosurgical procedure that is used to treat neurologic and
psychiatric disorders. Recent research in both animals and humans has shown that DBS may be
an effective procedure for refractory addiction. We previously propose to use DBS as treatment
for drug-seeking behaviors in a rat animal model, and found that high frequency DBS (HF-DBS)
of the ventral striatum/nucleus accumbens (VS/NAc) impaired extinction of morphine-induced
conditioned place preference (CPP), whereas low frequency DBS (LF-DBS) enhanced extinction
memory (reducing drug seeking behavior). Interestingly, we also found that LF-DBS
significatively shortens the persistency of the drug (LF-DBS~10 days vs sham-DBS~40 days). At
the molecular level, we found that DBS-treated animals increased BDNF expression in the
hippocampus (HPC). However, drug reinstatement was not significatively prevented in LF-DBS-
treated animals when stimulation was applied only during extinction sessions. In this transition
between the SCORE-SuRE grant cycle, we propose to further advance the knowledge in drug-
seeking behavior, and in the underlying DBS’ mechanisms of action, by using pharmacological
and chemogenetic approaches. Therefore, in the present study, Aim 1a-c will determine whether
LF-DBS applied during extinction, in addition to provide electrical stimulation in the phase of
drug reinstatement prevents drug seeking in a higher percentage of animals. Also, BDNF
expression will be measured in the HPC, as well as in other brain regions, i.e., amygdala, VS/NAc,
and medial prefrontal cortex (mPFC). Aim 2a will use a pharmacological approach by infusing
BDNF and TrkB antagonist (ANA-12) in the VS/NAc to determine their effects in extinction of
morphine CPP. Since glutamatergic neurons in the HPC encompass a subpopulation of neurons
expressing BDNF, the approach in Aim 2b is to use the chemogenetic tool, known as designer
receptors exclusively activated by designer drugs (DREADDs) to activate HPC glutamatergic
neurons in the presence of ANA-12, to prevent extinction of morphine CPP. Activation of
DREADDs will be done with clozapine N-oxide (CNO). Aim 2c will inactivate HPC-NAc
glutamatergic/BDNFergic projections that will prevent the beneficial effects of LF-DBS. Our
study represents a circuit-based approach to better understand the action mechanisms of drug-
seeking and extinction. Because rodent models of drug extinction resemble exposure-based
therapies in humans, it is possible that targeted electrical stimulation and the DBS-increased
expression of pro-extinction molecules might represent an effective future approach to reduce the
symptoms of addiction and opioid use disorders (OUD).
抽象/总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Jennifer Luz Barreto Estrada其他文献
Jennifer Luz Barreto Estrada的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Jennifer Luz Barreto Estrada', 18)}}的其他基金
G-RISE at the University of Puerto Rico Medical Sciences Campus
波多黎各大学医学科学校区的 G-RISE
- 批准号:
10558147 - 财政年份:2023
- 资助金额:
$ 14.9万 - 项目类别:
EFFECT OF ANDROGENS ON BEHAVIOR THROUGH NPY MODULATION
雄激素通过 NPY 调节对行为的影响
- 批准号:
8360152 - 财政年份:2011
- 资助金额:
$ 14.9万 - 项目类别:
CELLULAR AND MOLECULAR CHANGES ASSOCIATED WITH REPRODUCTIVE HEALTH
与生殖健康相关的细胞和分子变化
- 批准号:
8167857 - 财政年份:2010
- 资助金额:
$ 14.9万 - 项目类别:
CELLULAR AND MOLECULAR CHANGES ASSOCIATED WITH REPRODUCTIVE HEALTH
与生殖健康相关的细胞和分子变化
- 批准号:
7960056 - 财政年份:2009
- 资助金额:
$ 14.9万 - 项目类别:
CELLULAR AND MOLECULAR CHANGES ASSOCIATED WITH REPRODUCTIVE HEALTH
与生殖健康相关的细胞和分子变化
- 批准号:
7720870 - 财政年份:2008
- 资助金额:
$ 14.9万 - 项目类别:
CELLULAR AND MOLECULAR CHANGES ASSOCIATED WITH REPRODUCTIVE HEALTH
与生殖健康相关的细胞和分子变化
- 批准号:
7610164 - 财政年份:2007
- 资助金额:
$ 14.9万 - 项目类别:
相似海外基金
Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
- 批准号:
495434 - 财政年份:2023
- 资助金额:
$ 14.9万 - 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
- 批准号:
10642519 - 财政年份:2023
- 资助金额:
$ 14.9万 - 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
- 批准号:
10586596 - 财政年份:2023
- 资助金额:
$ 14.9万 - 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
- 批准号:
10590479 - 财政年份:2023
- 资助金额:
$ 14.9万 - 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
- 批准号:
23K06011 - 财政年份:2023
- 资助金额:
$ 14.9万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
- 批准号:
10682117 - 财政年份:2023
- 资助金额:
$ 14.9万 - 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
- 批准号:
10708517 - 财政年份:2023
- 资助金额:
$ 14.9万 - 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
- 批准号:
10575566 - 财政年份:2023
- 资助金额:
$ 14.9万 - 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
- 批准号:
23K15696 - 财政年份:2023
- 资助金额:
$ 14.9万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
- 批准号:
23K15867 - 财政年份:2023
- 资助金额:
$ 14.9万 - 项目类别:
Grant-in-Aid for Early-Career Scientists