The reinforcing and discriminative stimulus effects of orally administered MDMA
口服 MDMA 的强化和歧视刺激作用
基本信息
- 批准号:7817121
- 负责人:
- 金额:$ 36.53万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-05-01 至 2013-02-28
- 项目状态:已结题
- 来源:
- 关键词:AcuteAmphetaminesAreaBehavioralClinicalClinical TreatmentComplementDataDevelopmentDextroamphetamineDiscriminationDopamineDoseDrug usageFruitFutureGoalsHallucinogensHumanIntoxicationIntravenousInvestigationLaboratoriesLaboratory AnimalsMediatingMethodologyModelingNational Institute of Drug AbuseNeurotransmittersOralOrangesOverdosePapioPatternPeriodicityPharmaceutical PreparationsPharmacological TreatmentPharmacotherapyProbabilityProceduresPsychological reinforcementPsychotropic DrugsPublic HealthRelative (related person)ReportingResearchRodentRouteSelf AdministrationSelf-AdministeredSerotoninStimulusStimulus GeneralizationSystemTestingTrainingbasedrinkingdrug discriminationdrug of abuseecstasyexperienceimprovedinsightneurochemistrynon-drugnonhuman primatepre-clinicalreinforcerresearch studyresponsestimulant abuse
项目摘要
DESCRIPTION (provided by applicant): (1)-3, 4-methylenedioxymethamphetamine (MDMA, ecstasy) is a common drug of abuse that continues to be a public health concern. While the oral route of administration is the most common route used by recreational users, investigations of the reinforcing efficacy and subjective effects of MDMA have rarely used the oral route of MDMA administration. Development of an oral MDMA self-administration model, and a better understanding of how the subjective effects of orally administered MDMA are neurochemically mediated, in a species closely related to humans would significantly enhance our ability to develop pharmacotherapies intended to improve clinical treatment of MDMA abuse. Toward this goal, our first aim is to characterize the relative reinforcing efficacy of orally available MDMA in baboons in two experiments. First, reliable oral self-administration of MDMA will be engendered using a procedure that has been successful in previous studies of psychoactive compounds in baboons. A concentration-response function of orally available MDMA will be compared to vehicle, to d-amphetamine, and to a non-drug oral reinforcer (a fruit drink). In a second experiment, choice procedures will be used to compare multiple concentrations of MDMA to the other reinforcers. These studies will establish the methodology by which reliable, long-term oral MDMA self-administration can be studied experimentally in a nonhuman primate, will determine the range of concentrations across which reinforcement occurs, will determine whether cyclicity in pattern of self-administration develops across days, and will permit comparison to another commonly orally abused stimulant drug, as well as to a preferred non-drug oral reinforcer. Our second aim is to differentiate the discriminative stimulus effects and the neurochemical correlates of a low and a high dose of orally administered MDMA in baboons by use of multiple-dose discrimination procedures. The putatively differential neurochemical changes that occur as a function of lower and higher doses of MDMA administration will be investigated using drug substitution and antagonism testing in baboons trained to discriminate a low or a high dose of MDMA, and then when the baboons are discriminating both doses. We anticipate the discriminative stimulus effects of a low dose of MDMA will differ significantly from those of a high dose of MDMA, as evidenced by the generalization and antagonism profiles for each training dose. These data will be important to our understanding of the extent to which neurochemical mechanisms are mirrored in subjective drug effects in general and for MDMA in particular. The distinguishing features of our proposal are the use of the oral route of MDMA administration under well-controlled laboratory conditions in baboons, and the use of multiple training doses in the investigation of the discriminative stimulus effects of MDMA in baboons. Our proposal will generate data fundamental to the future development of pharmacotherapies for MDMA abuse, thereby contributing to our long-term goal of facilitating treatment of MDMA intoxication, overdose, and use/abuse.
描述(由申请人提供):(1)- 3,4 -亚甲基二氧基甲基苯丙胺(MDMA,摇头丸)是一种常见的滥用药物,仍然是公共卫生问题。虽然口服给药途径是娱乐性使用者最常用的途径,但对MDMA强化功效和主观效应的研究很少采用口服给药途径。开发一种口服MDMA自我给药模型,以及更好地了解口服MDMA的主观效应是如何在与人类密切相关的物种中通过神经化学介导的,将大大提高我们开发药物疗法的能力,旨在改善MDMA滥用的临床治疗。为了实现这一目标,我们的第一个目标是在两个实验中表征口服MDMA在狒狒中的相对强化功效。首先,可靠的口服自我给药MDMA将产生的程序,已在以前的研究中成功的精神活性化合物在狒狒。将口服MDMA的浓度-反应函数与对照剂、d-安非他明和非药物口服强化剂(果汁饮料)进行比较。在第二个实验中,选择程序将用于比较多种浓度的MDMA和其他强化剂。这些研究将建立可靠的、长期口服MDMA自我给药的方法,可以在非人类灵长类动物中进行实验研究,将确定强化发生的浓度范围,将确定自我给药模式的周期性是否在几天内发展,并将允许与另一种常用的口服兴奋剂药物进行比较,以及优选的非药物口服强化剂。我们的第二个目标是通过使用多剂量区分程序来区分低剂量和高剂量口服MDMA对狒狒的区别刺激效应和神经化学相关。研究人员将在训练狒狒分辨低剂量或高剂量MDMA的过程中,通过药物替代和拮抗试验,以及当狒狒分辨两种剂量时,对低剂量和高剂量MDMA所产生的神经化学变化进行研究。我们预计,低剂量MDMA的区别性刺激效应将与高剂量MDMA的区别性刺激效应显著不同,这可以从每次训练剂量的泛化和拮抗概况中得到证明。这些数据对于我们理解神经化学机制在多大程度上反映在主观药物效应中,特别是MDMA,将是非常重要的。我们的建议的显著特点是在控制良好的实验室条件下,在狒狒中使用口服MDMA给药途径,并在研究MDMA对狒狒的区别刺激效应时使用多重训练剂量。我们的建议将为MDMA滥用药物治疗的未来发展提供基础数据,从而有助于我们促进MDMA中毒,过量和使用/滥用治疗的长期目标。
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 }}
Nancy A. Ator其他文献
Behavioral Biology
- DOI:
10.1007/bf03391936 - 发表时间:
2017-06-01 - 期刊:
- 影响因子:3.800
- 作者:
Nancy A. Ator - 通讯作者:
Nancy A. Ator
The influence of stimulus uncertainty and experimental instructions on visual selection
- DOI:
10.3758/bf03209542 - 发表时间:
1969-05-01 - 期刊:
- 影响因子:1.700
- 作者:
Terry T. Faw;Jum C. Nunnally;Nancy A. Ator - 通讯作者:
Nancy A. Ator
Nancy A. Ator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('Nancy A. Ator', 18)}}的其他基金
The reinforcing and discriminative stimulus effects of orally administered MDMA
口服 MDMA 的强化和歧视刺激作用
- 批准号:
7371392 - 财政年份:2008
- 资助金额:
$ 36.53万 - 项目类别:
The reinforcing and discriminative stimulus effects of orally administered MDMA
口服 MDMA 的强化和歧视刺激作用
- 批准号:
8261993 - 财政年份:2008
- 资助金额:
$ 36.53万 - 项目类别:
FUNCTIONAL ANALYSIS OF GABAERGIC SEDATIVE/ANXIOLYTICS
伽巴能镇静/抗焦虑药的功能分析
- 批准号:
7716156 - 财政年份:2008
- 资助金额:
$ 36.53万 - 项目类别:
The reinforcing and discriminative stimulus effects of orally administered MDMA
口服 MDMA 的强化和歧视刺激作用
- 批准号:
7616801 - 财政年份:2008
- 资助金额:
$ 36.53万 - 项目类别:
The reinforcing and discriminative stimulus effects of orally administered MDMA
口服 MDMA 的强化和歧视刺激作用
- 批准号:
8067923 - 财政年份:2008
- 资助金额:
$ 36.53万 - 项目类别:
GABA-A alpha5 cognitive enhancers: pharmacology and neuropsychology in macaques
GABA-A α5 认知增强剂:猕猴的药理学和神经心理学
- 批准号:
7486744 - 财政年份:2007
- 资助金额:
$ 36.53万 - 项目类别:
GABA-A alpha5 cognitive enhancers: pharmacology and neuropsychology in macaques
GABA-A α5 认知增强剂:猕猴的药理学和神经心理学
- 批准号:
7916676 - 财政年份:2007
- 资助金额:
$ 36.53万 - 项目类别:
GABA-A alpha5 cognitive enhancers: pharmacology and neuropsychology in macaques
GABA-A α5 认知增强剂:猕猴的药理学和神经心理学
- 批准号:
7675260 - 财政年份:2007
- 资助金额:
$ 36.53万 - 项目类别:
GABA-A alpha5 cognitive enhancers: pharmacology and neuropsychology in macaques
GABA-A α5 认知增强剂:猕猴的药理学和神经心理学
- 批准号:
8132922 - 财政年份:2007
- 资助金额:
$ 36.53万 - 项目类别:
相似海外基金
Relationship between neurotoxicity and the chemical structures of amphetamines
安非他明的神经毒性与化学结构的关系
- 批准号:
25860103 - 财政年份:2013
- 资助金额:
$ 36.53万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Search for protein expression in amphetamines treated mouse heart : Challenge to the diagnosis for the sudden death of amphetamines abusers
寻找安非他明治疗小鼠心脏中的蛋白质表达:对安非他明滥用者猝死诊断的挑战
- 批准号:
22659138 - 财政年份:2010
- 资助金额:
$ 36.53万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Novel Functionally-Selective Serotonin 5HT2 Drugs for Amphetamines Abuse/Disorder
用于治疗安非他明滥用/疾病的新型功能选择性血清素 5HT2 药物
- 批准号:
8312648 - 财政年份:2010
- 资助金额:
$ 36.53万 - 项目类别:
Novel Functionally-Selective Serotonin 5HT2 Drugs for Amphetamines Abuse/Disorder
用于治疗安非他明滥用/疾病的新型功能选择性血清素 5HT2 药物
- 批准号:
8531900 - 财政年份:2010
- 资助金额:
$ 36.53万 - 项目类别:
Novel Functionally-Selective Serotonin 5HT2 Drugs for Amphetamines Abuse/Disorder
用于治疗安非他明滥用/疾病的新型功能选择性血清素 5HT2 药物
- 批准号:
8715749 - 财政年份:2010
- 资助金额:
$ 36.53万 - 项目类别:
Novel Functionally-Selective Serotonin 5HT2 Drugs for Amphetamines Abuse/Disorder
用于治疗安非他明滥用/疾病的新型功能选择性血清素 5HT2 药物
- 批准号:
8144930 - 财政年份:2010
- 资助金额:
$ 36.53万 - 项目类别:
Translational Genetics and Dopamine Signaling in Sensitivity to Amphetamines
安非他明敏感性中的转化遗传学和多巴胺信号传导
- 批准号:
7675601 - 财政年份:2009
- 资助金额:
$ 36.53万 - 项目类别:
Simultaneous determination of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates and interaction in the rat
大鼠体内麻黄碱、安非他明、可卡因、可卡因代谢物和阿片类药物的同时测定及其相互作用
- 批准号:
17590585 - 财政年份:2005
- 资助金额:
$ 36.53万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Study for practical use of two chiral analyses of amphetamines by gas chromatography-mass spectrometry
气相色谱-质谱法对苯丙胺两种手性分析的实用化研究
- 批准号:
17590588 - 财政年份:2005
- 资助金额:
$ 36.53万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Clinical Pharmacology of 3,4-Methylenedioxy Amphetamines
3,4-亚甲二氧基安非他明的临床药理学
- 批准号:
6870119 - 财政年份:2004
- 资助金额:
$ 36.53万 - 项目类别: