Unpredictable availability as a determinant of drug-related outcomes

不可预测的可用性是药物相关结果的决定因素

基本信息

批准号：
10360602
负责人：
Sally Huskinson
金额：
$ 36.81万
依托单位：
UNIVERSITY OF MISSISSIPPI MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2025-03-31
项目状态：
未结题

项目摘要

Project Summary Unpredictable drug access may play an important role in drug abuse. We know from laboratory studies that behavior maintained by nondrugs such as food is more persistent with unpredictable (i.e., variable) schedules of availability than with predictable (i.e., fixed) schedules, and nonhuman subjects choose a variable option over a fixed one even when it costs more in terms of responses per delivery. We recently found that rhesus monkeys choose variable cocaine over a fixed cocaine option, extending work with nondrug reinforcers to a drug of abuse. In addition, we have preliminary data showing that a history of responding for cocaine injections under a variable schedule increases cocaine self-administration under a progressive-ratio schedule. Thus, we predict that unpredictable access to drugs of abuse is an important determinant of the choice to take a drug at the expense of nondrug alternatives and that a history of unpredictable drug access can in- crease the reinforcing effectiveness of drugs. In Specific Aim 1, we will use drug vs. nondrug choice to evaluate the prediction that cocaine choice will be greatest when it is delivered under an unpredictable sched- ule and food under a predictable schedule. Conversely, cocaine choice will be decreased when food is deliv- ered under an unpredictable schedule and cocaine under a predictable schedule. Confirmation of our hypothe- ses would indicate that unpredictable availability contributes to excessive allocation of behavior toward procur- ing drugs at the expense of more predictable, nondrug alternatives. If unpredictable food delivery decreases cocaine choice, it would support the use of novel and easily implemented modifications to therapies like con- tingency management or treatments that incorporate nondrug reinforcers. In Specific Aim 2 we hypothesize that long-term exposure to a variable schedule of cocaine delivery will increase the effectiveness of cocaine as a reinforcer relative to a period of fixed cocaine exposure, and this effect will be enhanced with a more unpre- dictable VR compared to a more predictable VR. Confirmation of this prediction would indicate that unpredicta- bility is a contributing factor to the perseverative drug-seeking behavior seen in cocaine-dependent individuals. The data collected in this aim will allow us to evaluate whether placing drug reinforcers under more predictable schedules (as is experienced with agonist replacement therapy) can reduce some of the deleterious effects of a history of unpredictable access. A reduction in adverse consequences engendered by a switch from unpre- dictable to predictable schedules may represent a behavioral mechanism underlying agonist replacement ther- apies. Conversely, we will be able to evaluate whether placing a drug with a history of predictable access un- der unpredictable-access conditions exacerbates drug-seeking behavior, which would have implications for effects of discontinuing agonist replacement therapy or prescription drug availability which would represent a transition from predictable drug access to unpredictable drug access (i.e., returning to illicit drug use).

项目摘要不可预测的药物获取可能在药物滥用中起重要作用。我们从实验室研究中知道不可预测的（即变量）时间表，诸如食物之类的非食品（例如食物）维护的行为更加持久可用性比可预测的（即固定）时间表和非人类主题选择变量选项在固定的响应方面，即使在一个固定的响应方面成本更高。我们最近发现恒河猴子选择可卡因，而不是固定可卡因选项，将与Nondrug增强剂的工作扩展到滥用药物。此外，我们还有初步数据表明，可卡因注射的史在可变的时间表下，在渐进式比率计划下增加了可卡因的自我管理。那，我们预测，不可预测的滥用药物是选择的重要决定因素毒品以非药物的替代为代价，并且不可预测的药物获取历史可以说折痕药物的增强有效性。在特定的目标1中，我们将使用药物与Nondrug选择评估可卡因选择在不可预测的时间表下交付时最大的预测将是根据可预测的时间表。相反，食物熟食时可卡因的选择将减少根据无法预测的时间表和可卡因在可预测的时间表下进行。确认我们的假设 SES会表明，不可预测的可用性导致行为分配过多以更可预测的非降r替代品为代价。如果不可预测的食物送货会下降可卡因的选择，它将支持对诸如疗法的疗法的新颖和轻松实施的修改刺激性管理或融合了非果钢筋的治疗方法。在特定目标2中，我们假设长期接触可卡因的可变时间表将提高可卡因的有效性相对于固定可卡因暴露时期的增强剂，这种影响将得到增强与更可预测的VR相比，可有效的VR。对该预测的确认将表明未预测能力是可卡因依赖性个体中持续的寻求毒品行为的促成因素。此目标中收集的数据将使我们能够评估是否将药物增强剂放置在更可预测的下时间表（按照激动剂替代疗法经历）可以减少某些有害影响不可预测的访问历史。提前减少的后果是由未经未来的转换带来的可预测的时间表可能代表了激动剂替代治疗基础的行为机制猿。相反，我们将能够评估是否将具有可预测史的药物放置无法预测的访问条件加剧了寻求毒品的行为，这将对停用激动剂替代疗法或处方药的可用性的影响，这将代表从可预测的药物进入无法预测的药物获取（即返回非法药物使用）的过渡。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Applied Quantitative Analysis of Behavior: What It Is, and Why We Care-Introduction to the Special Section.

行为的应用定量分析：它是什么，以及我们为什么关心 - 特别部分介绍。

DOI：
10.1007/s40614-021-00323-w
发表时间：
2021
期刊：
Perspectives on behavior science
影响因子：
2
作者：
Jarmolowicz,DavidP;Greer,BrianD;Killeen,PeterR;Huskinson,SallyL
通讯作者：
Huskinson,SallyL

Unpredictability as a modulator of drug self-administration: Relevance for substance-use disorders.

作为药物自我给药调节剂的不可预测性：与物质使用障碍的相关性。

DOI：
10.1016/j.beproc.2020.104156
发表时间：
2020
期刊：
Behavioural processes
影响因子：
1.3
作者：
Huskinson,SallyL
通讯作者：
Huskinson,SallyL

Challenges to Conducting Contingency Management Treatment for Substance Use Disorders: Practice Recommendations for Clinicians.

DOI：
10.1037/pro0000356
发表时间：
2021-04
期刊：
Professional psychology, research and practice
影响因子：
0
作者：
Pfund RA;Cook JE;McAfee NW;Huskinson SL;Parker JD
通讯作者：
Parker JD

The G-protein biased kappa opioid agonists, triazole 1.1 and nalfurafine, produce non-uniform behavioral effects in male rhesus monkeys.

DOI：
10.1016/j.pbb.2022.173394
发表时间：
2022-06
期刊：
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
影响因子：
3.6
作者：
Huskinson, Sally L.;Platt, Donna M.;Zamarripa, C. Austin;Dunaway, Kristen;Brasfield, Morgan;Prisinzano, Thomas E.;Blough, Bruce E.;Freeman, Kevin B.
通讯作者：
Freeman, Kevin B.