Individual differences & cocaine effects on impulsive choice in rats: D3/5HT1B
个体差异
基本信息
- 批准号:9891993
- 负责人:
- 金额:$ 37.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-07-01 至 2022-05-31
- 项目状态:已结题
- 来源:
- 关键词:AbstinenceAddictive BehaviorAffinityAgonistBehaviorBehavioralBrainBrain regionChoice BehaviorChronicClinical ResearchCocaineCocaine DependenceComplementCorpus striatum structureDataDecision MakingDevelopmentDiseaseDopamineDrug AddictionDrug usageEtiologyExhibitsFunctional Magnetic Resonance ImagingFunctional disorderFutureHumanImageImpairmentImpulsive BehaviorImpulsivityIndividualIndividual DifferencesLeadMeasurementMeasuresMediatingMidbrain structurePathologicPharmaceutical PreparationsPharmacologyPositron-Emission TomographyPrefrontal CortexProceduresProcessRattusResearchRewardsRiskRoleSelf AdministrationSerotoninSignal TransductionStructureSymptomsSystemTIRAP geneTestingTracerValidationVariantVentral Striatumaddictionbiobehaviorcocaine exposurecocaine usediscountdiscountingflexibilityin vivolongitudinal positron emission tomographymonoaminemultimodalityneurobiological mechanismneurochemistryneuroimagingnonhuman primatepeerpre-clinical researchreceptorreceptor bindingreceptor densityrelating to nervous system
项目摘要
Although many people engage in occasional drug use, few become drug-dependent. The mechanisms
by which addiction vulnerability and drug-induced pathological factors interact to increase the likelihood of drug
dependence remain unknown. Mounting evidence suggests that drug dependence is strongly associated with
dysfunctional impulsive decision-making processes in which individuals with cocaine-use disorder (CUD)
undervalue (Le., discount) future rewards in favor of smaller, immediate rewards to a greater extent than their
non-addicted peers. Thus, temporal discounting of reward, as measured by various intertemporal choice tasks,
has been proposed as a behavioral marker of addiction, which may be due to aberrant dopamine (DA) and
serotonin (5HT) signaling within midbrain regions and corticostriatal circuits including the ventromedial
prefrontal cortex (vmPFC) and striatum. Studies in CUD show elevated D3 receptor availability in the midbrain,
decreased 5HT1B availability in the vmPFC and heightened levels of impulsive choice. Furthermore, our pilot
rat positron emission tomography (PET) data demonstrate increased striatal l1C-PHNO binding is positively
correlated with subsequent cocaine self-administration and individual differences in choice behavior, which
highlights the impact of vulnerability factors on cocaine use. We have also shown that D2I3 receptors modulate
flexible decision-making but it is not known how these receptors impact impulsive choice or cocaine self-
administration. Here we will use a delay discounting across various randomly presented delays procedure,
which yields robust individual differences in rat temporal discounting, in combination with two PET tracers (11C-
PHNO for D3 and 11C-P943 for 5HT18 receptors), receptor-specific pharmacology and cocaine self-
administration to investigate these proposed biobehavioral markers of addiction.
In Aim 1, we will investigate the relationship between individual differences in corticostriatal D3 and
5HT1B receptors and impulsive choice and cocaine self-administration. In Aim 2, we will assess the impact of
cocaine self-administration on corticostriatal D3 and 5HT18 receptors and impulsive choice using longitudinal
PET/behavioral analyses and ex vivo analyses. Finally, in Aim 3, we will determine the role of midbrain D3 and
vmPFC 5HT18 receptor regulated signaling in cocaine-induced enhancements in impulsive choice. In
accordance with pre-clinical and clinical research, we predict that individual differences in impulsive choice are
mediated by vmPFC 5HT1Band that cocaine induced-changes of midbrain D3 receptors modulates this
signaling, yielding enhancements in impulsivity. Our studies in rats will complement studies in CUD individuals
through the use of longitudinal neuroimaging, pharmacological manipulation of brain targets, and ex vivo
validation of PET imaging results, while maintaining the common behavioral metric of impulsive choice.
虽然许多人偶尔吸毒,但很少有人对毒品产生依赖。的机制
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)
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Jane R Taylor其他文献
Sex chromosome complement regulates habit formation
性染色体组型调节习惯形成
- DOI:
10.1038/nn1994 - 发表时间:
2007-10-21 - 期刊:
- 影响因子:20.000
- 作者:
Jennifer J Quinn;Paul K Hitchcott;Elizabeth A Umeda;Arthur P Arnold;Jane R Taylor - 通讯作者:
Jane R Taylor
Repeated, Intermittent Δ9-Tetrahydrocannabinol Administration to Rats Impairs Acquisition and Performance of a Test of Visuospatial Divided Attention
对大鼠重复、间歇性给予Δ9-四氢大麻酚会损害其对视觉空间分配注意测试的习得和表现
- DOI:
10.1038/sj.npp.1300316 - 发表时间:
2003-08-26 - 期刊:
- 影响因子:7.100
- 作者:
Christopher D Verrico;J David Jentsch;Robert H Roth;Jane R Taylor - 通讯作者:
Jane R Taylor
Jane R Taylor的其他文献
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{{ truncateString('Jane R Taylor', 18)}}的其他基金
Memory Destabilization and Cocaine-Cue Induced Reinstatement in Rat
大鼠记忆不稳定和可卡因诱导的恢复
- 批准号:
10599998 - 财政年份:2021
- 资助金额:
$ 37.7万 - 项目类别:
Memory Destabilization and Cocaine-Cue Induced Reinstatement in Rat
大鼠记忆不稳定和可卡因诱导的恢复
- 批准号:
10293792 - 财政年份:2021
- 资助金额:
$ 37.7万 - 项目类别:
Memory Destabilization and Cocaine-Cue Induced Reinstatement in Rat
大鼠记忆不稳定和可卡因诱导的恢复
- 批准号:
10441536 - 财政年份:2021
- 资助金额:
$ 37.7万 - 项目类别:
Individual Differences & Cocaine Effects on Impulsive Choice in Rat
个体差异
- 批准号:
10618290 - 财政年份:2016
- 资助金额:
$ 37.7万 - 项目类别:
Individual Differences & Cocaine Effects on Impulsive Choice in Rat
个体差异
- 批准号:
10361717 - 财政年份:2016
- 资助金额:
$ 37.7万 - 项目类别:
Individual differences & cocaine effects on impulsive choice in rats: D3/5HT1B
个体差异
- 批准号:
9282946 - 财政年份:2016
- 资助金额:
$ 37.7万 - 项目类别:
Cocaine, Impulsivity, and Stratal Function in Rats
可卡因、冲动和大鼠的层层功能
- 批准号:
7797707 - 财政年份:2010
- 资助金额:
$ 37.7万 - 项目类别:
Sex Differences in Alcohol Habit Formation in Rats: Corticostriatal Mechanisms
大鼠饮酒习惯形成的性别差异:皮质纹状体机制
- 批准号:
7528657 - 财政年份:2008
- 资助金额:
$ 37.7万 - 项目类别:
Sex Differences in Alcohol Habit Formation in Rats: Corticostriatal Mechanisms
大鼠饮酒习惯形成的性别差异:皮质纹状体机制
- 批准号:
7658974 - 财政年份:2008
- 资助金额:
$ 37.7万 - 项目类别:
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