NOP Receptors in nonhuman primate models of AUD
AUD 非人灵长类动物模型中的 NOP 受体
基本信息
- 批准号:10212896
- 负责人:
- 金额:$ 50.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-10 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAdolescentAdultAdverse effectsAffectAgonistAlcohol abuseAlcohol consumptionBehavioralBrainBrain imagingBuprenorphineCatalogsChronicDataDoseEthanolFemaleFoodHeavy DrinkingHourHusbandImaging TechniquesIndividualLaboratoriesLong-Term EffectsMacaca mulattaMeasuresMethodsModelingMonitorMonkeysNational Institute on Alcohol Abuse and AlcoholismORL1 receptorOpioid PeptideParentsPeptide ReceptorPeptidesPharmaceutical PreparationsPharmacologyPharmacotherapyPhenotypePositron-Emission TomographyProceduresPublic HealthRecoveryResearchResearch PersonnelRodent ModelRoleRunningScanningSex DifferencesStrategic PlanningTestingTimeTimeLinealcohol abstinencealcohol availabilityalcohol sensitivityalcohol use disorderbasechronic alcohol ingestionclinically relevantcostdesigndrinkingdrug developmentdrug efficacyefficacious treatmentimaging studyindexingmalenociceptinnonhuman primatenovelnovel therapeuticspreclinical studyradiotracerreceptorresearch clinical testingresponseside effecttranslational approachtranslational modeltranslational study
项目摘要
PROJECT SUMMARY.
Alcohol use disorder (AUD) persists as a costly public health problem that lacks widely effective medications.
The scientific premise of the proposed research is that brain receptors for the nociceptin/orphanin FQ peptide
(NOP) are promising targets for new medications, but translational studies in sophisticated nonhuman primate
(NHP) models are needed to inform and direct drug development and clinical testing. This premise is based on
encouraging data from rodent models and positive preliminary data from our NHP laboratory using
buprenorphine and its derivative BU08028, termed a “bifunctional” MOP/NOP agonist because it stimulates
both NOP and mu opioid peptide (MOP) receptors. The proposed studies combine a well-characterized,
clinically relevant NHP model of chronic ethanol (EtOH) drinking, novel NOP- and MOP/NOP-acting drugs, a
translational method of pharmacotherapy assessment and noninvasive brain imaging using positron emission
tomography (PET imaging). After being induced to drink EtOH using established procedures, male and female
rhesus monkeys will have free access to EtOH; responding to receive food pellets will also be monitored as an
index of potential side effects. Specific Aim 1 will determine the effects of buprenorphine and its derivative
BU08028, in combination with drugs that selectively stimulate or block MOP or NOP receptors. The results will
reveal the relative contribution of MOP and NOP receptor stimulation to the ability of bifunctional agonists to
decrease EtOH drinking, indicating the ideal pharmacological profile for a medication. Next (Aim 2), drugs that
possess the desired profile will be selected from among a catalog of novel compounds synthesized by Co-
Investigator Dr. Stephen Husbands. Candidates will be administered daily for several months and effects on
moderate and heavy drinking (6 or 22 hours per day, respectively) will be determined using a translational
approach developed by the P.I. We expect to identify a compound that produces prolonged suppression of
EtOH drinking without altering food-maintained responding or producing adverse effects. Aim 3 consists of
PET imaging studies using the novel radiotracer [11C]NOP-1A that run parallel to Aims 1 and 2. These studies
will characterize (1) the influence of basal NOP receptor availability on initial sensitivity to EtOH, (2) the effects
of long-term EtOH drinking on NOP receptors, (3) the effects of efficacious treatments on NOP receptor
availability, (4) the extent of recovery of NOP receptor availability during abstinence from EtOH and,
importantly, (5) sex differences in all these measures. Together, the results of these studies will provide novel,
translational data to support the feasibility and efficacy of developing MOP/NOP and NOP-selective agonists
as novel AUD pharmacotherapies using translational, clinically relevant NHP models.
项目总结。
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)
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Paul W. Czoty其他文献
Effects of chronic alcohol consumption on cocaine self-administration in rhesus monkeys
- DOI:
10.1016/j.drugalcdep.2014.09.161 - 发表时间:
2015-01-01 - 期刊:
- 影响因子:
- 作者:
Paul W. Czoty - 通讯作者:
Paul W. Czoty
Effect of menstrual phase and social stress on cognitive performance of female monkeys
- DOI:
10.1016/j.drugalcdep.2014.09.365 - 发表时间:
2015-01-01 - 期刊:
- 影响因子:
- 作者:
Sarah A. Kromrey;Paul W. Czoty;Michael A. Nader - 通讯作者:
Michael A. Nader
Effects of the dopamine D3/D2 receptor antagonist buspirone on food/cocaine choice in socially housed male cynomolgus monkeys
- DOI:
10.1016/j.drugalcdep.2014.09.144 - 发表时间:
2015-01-01 - 期刊:
- 影响因子:
- 作者:
Michael Coller;Paul W. Czoty;Michael A. Nader - 通讯作者:
Michael A. Nader
Dopamine D3 receptor availability: Sex differences and effects of chronic drug exposure
- DOI:
10.1016/j.drugalcdep.2014.09.442 - 发表时间:
2015-01-01 - 期刊:
- 影响因子:
- 作者:
Susan Martelle;Susan H. Nader;Paul W. Czoty;William S. John;Amy H. Newman;Michael A. Nader - 通讯作者:
Michael A. Nader
Influence of reproductive hormones on social rank and vulnerability to cocaine reinforcement in female cynomolgus monkeys
- DOI:
10.1016/j.drugalcdep.2015.07.331 - 发表时间:
2015-11-01 - 期刊:
- 影响因子:
- 作者:
Sarah Kromrey;Paul W. Czoty;Michael A. Nader - 通讯作者:
Michael A. Nader
Paul W. Czoty的其他文献
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{{ truncateString('Paul W. Czoty', 18)}}的其他基金
NOP Receptors in nonhuman primate models of AUD
AUD 非人灵长类动物模型中的 NOP 受体
- 批准号:
10386932 - 财政年份:2020
- 资助金额:
$ 50.26万 - 项目类别:
NOP Receptors in nonhuman primate models of AUD
AUD 非人灵长类动物模型中的 NOP 受体
- 批准号:
10608164 - 财政年份:2020
- 资助金额:
$ 50.26万 - 项目类别:
NOP Receptors in nonhuman primate models of AUD
AUD 非人灵长类动物模型中的 NOP 受体
- 批准号:
9885081 - 财政年份:2020
- 资助金额:
$ 50.26万 - 项目类别:
Project 2: Mechanisms underlying vulnerability to ethanol self-administration: behavioral and brain imaging studies in group-housed monkeys
项目 2:乙醇自我管理脆弱性的潜在机制:群养猴子的行为和大脑成像研究
- 批准号:
10310701 - 财政年份:2017
- 资助金额:
$ 50.26万 - 项目类别:
Project 2: Mechanisms underlying vulnerability to ethanol self-administration: behavioral and brain imaging studies in group-housed monkeys
项目 2:乙醇自我管理脆弱性的潜在机制:群养猴子的行为和大脑成像研究
- 批准号:
10526644 - 财政年份:2017
- 资助金额:
$ 50.26万 - 项目类别:
Interactions of Ethanol & Cocaine Self-Administration in Monkeys
乙醇的相互作用
- 批准号:
9502948 - 财政年份:2016
- 资助金额:
$ 50.26万 - 项目类别:
Interactions of Ethanol & Cocaine Self-Administration in Monkeys
乙醇的相互作用
- 批准号:
9175685 - 财政年份:2016
- 资助金额:
$ 50.26万 - 项目类别:
Brain imaging and cognitive effects of cocaine self-administration in monkeys
猴子自我注射可卡因的脑成像和认知效应
- 批准号:
7867262 - 财政年份:2010
- 资助金额:
$ 50.26万 - 项目类别:
Cocaine discrimination, self-administration and microdialysis in monkeys
猴子可卡因歧视、自我给药和微透析
- 批准号:
7877863 - 财政年份:2007
- 资助金额:
$ 50.26万 - 项目类别:
Cocaine discrimination, self-administration and microdialysis in monkeys
猴子可卡因歧视、自我给药和微透析
- 批准号:
7259129 - 财政年份:2007
- 资助金额:
$ 50.26万 - 项目类别:
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